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Smart Drugs (nootropics)

More Questions answered

I received this in an email concerning this thread:

>Deprenyl is a great example of a nootropics by its
> numerous benefits. Thus making it one of the most popular prescription drugs
> in the cognitive enhancement field. This drug is also known as L-deprenyl
> and selegiline and is one of the most widely researched nootropics for
> nearly forty years with over two hundred research papers on it.
> Selegiline works by preserving the brain as a protector and a neuro-rescue
> agent in times of stress and injury while being an antidepressant and
> cognitive enhancement agent.

Perhaps? But terms such as “protector” are vague. Gotta get more
specific on what it does?

Here is the best answer I could come up with as the Neuro-protector.

DPR has been shown to protect nerve cells from an ever-growing list of neurotoxins. Some of these neurotoxins can actually be produced within the brain under certain conditions, while others come from the environment or diet.
MPTP is a chemical first identified as a contaminant in synthetic heroin. In the 1980s young men using synthetic heroin suddenly developed a Parkinson-like disease. It was then discovered that the MPTP was taken up by glial cells surrounding nigrostriatal neurons, where it was converted by glial MAO-B enzymes into the real toxin, MPP+. The nigral neurons then absorbed MPP+ into their mitochondria, where MPP+ poisoned the mitochondria, killing the DA-using neurons.(15) The MAO-B inhibiting dose of DPR (10 mg/day) has been shown to prevent MPTP from being converted to the neurotoxin MPP+.(4) And as Lange and colleagues note, Compounds with a chemical structure similar to MPTP include both natural and synthetic products (e.g. paraquat) that are used in agriculture! (15)
6-hydroxydopamine (6-OHDA) is a potent neurotoxin that can spontaneously form from DA in DA-using neurons. (11,13) 6-OHDA may then further auto-oxidize to generate toxic superoxide and hydroxyl free radicals and hydrogen peroxide. (11,13) Knolls research has shown that pre-treatment of striatal DA-neurons with DPR can completely protect them from 6-OHDA toxicity. (4,11,13) Even in those not suffering from Parkinsons disease, the nigrostriatal neurons are the fastest aging neuron population in the human brain - an average 13% loss every decade from the 40s on. (1,13) Knoll and others believe that 6-OHDA neurotoxicity is a key cause of this normal nigral death, and that DPR may be just what the doctor ordered to retard this debilitating downhill neural slide.
DSP-4 is a synthetic NA-nerve toxin. In rodents DPR has been shown to prevent the depletion of NA in NA-using neurons and NA-nerve degeneration that DSP-4 causes. (4) AF64A is a cholinergic toxin - it damages brain cells that use acetylcholine. DPR pre-treatment has been shown to protect cholinergic neurons from AF64A toxicity. (4)
DPR has also protected human nerve cells from peroxynitrite and nitric oxide toxicity. Peroxynitrite is formed naturally in the brain when nitric oxide reacts with superoxide radical. Peroxynitrite causes apoptosis, a programmed suicide cell death that can be triggered in neurons by various agents. DPR was found to inhibit peroxynitrite-caused apoptosis, even after the DPR was washed from DPR pre-treated cells. (3)
Methyl-salsolinol is another MAO-B produced endogenous neurotoxin. Salsolinol is a tetra-hydroisoquinoline produced from the interaction of DA and acetaldehyde, the first-stage breakdown product of alcohol.
Once formed, salsolinol can then be further modified by MAO-B to generate methyl-salsolinol. DPRs MAO-B inhibiting activity can prevent the DNA damage caused by this toxin. (3,4)
By inhibiting MAO-B, DPR reduces the toxic load on the brain that is routinely produced through the normal operation of MAO-B. MAO-B digests not just DA and PEA, but also tryptamine, tyramine and various other secondary and tertiary amines. (15)
As noted earlier, PEA is the substance MAO-B is most efficient at digesting, so that the half-life of PEA is estimated at only 0.4 minutes. (21)
This continuous high level breakdown of PEA (and other amines) produces aldehydes, hydrogen peroxide and ammonia as automatic MAO-B reaction products, and they are all toxins. (4) Thus by reducing age-elevated MAO-B activity, DPR reduces the toxin burden on DA/NA neurons (where PEA is primarily produced).
…L-deprenyl provides neuroprotection against growth factor withdrawal in PC12 cells, oxidative stress in mesencepahalic neurons, and the genotoxic compound, Ara C, in cerebellar granule neurons, and against axotomy-induced motoneuronal degeneration and delayed neuronal death in hippocampus after global ischaemia. (24) And these are just some of the many reports in the scientific literature on DPRs versatile neuroprotection.

The answer came from this website, so you can check the references if you wish.….E=&TOPIC_ID=582

“You see, I don’t want to do good things, I want to do great things.” ~Alexander Joseph Luthor

I know Lewd Ferrigno personally.


GalantaMind is Galantamine hydrobromide extract from the Spider Lily plant (Lycoris radiata.) It is also found in other plants such as the Daffodil and the Snowdrop plant. Each capsule contains: Galantamine hydrobromide extract, Vitamin B5, and Choline.

Around 3,200 years ago the Greek adventurer Ulysses (Odysseus) had a problem. The witch, Circe, had bewitched his crew with a potion that made them forgetful and delusional. According to one researcher, Ulysses rescued his crew from their altered state with an antidote made from the Snowdrop plant, and it contained Galantamine.

We generally don’t have these kinds of problems these days but we do have memory problems and in extreme cases, Alzheimer’s Disease (AD.) Current prescription drugs such as Cognex®, Aricept®, and Exelon®, which are used for this condition are Acetylcholinesterase (AChE) inhibitors. Acetylcholine, vital to memory, is the neurotransmitter that is damaged most in AD and AChE worsens the problem by destroying it. This is a normal part of brain function for a healthy person since you don’t want acetylcholine building up too much, but for an AD patient it is crippling since they don’t have enough as it is. They may have lost as much as 90% of their acetylcholine.

The problem with these drugs is that they provide some temporary relief from the symptoms of AD but lose their effectiveness within a year. They can also cause serious side effects ranging from liver damage to seizures and depression.

Galantamine is also an AChE inhibitor but is quite different in several respects:

1. While other prescription medicines desensitize the receptors in the brain rendering them useless usually within a year, Galantamine does not do so and can be used for a much longer time.

2. Galantamine goes beyond acetylcholine by also regulating the release of other neurotransmitters such as glutamate, GABA and Serotonin, all vital to memory.

3. It enhances the action of nicotinic receptors in the brain, which no other prescription drug does. This is a special class of acetylcholine receptors that enhance cerebral blood flow as well as cognitive and psychomotor functions. Healthy nicotinic receptors are also though to inhibit beta-amyloid plaque formation, implicated in AD.

4. It boosts the production of new acetylcholine neurotransmitters in the brain.
This substance is now a FDA approved prescription drug called Reminyl® (Feb 2001). How much do you suppose they are charging for this natural substance?


May cause nausea, vomiting or diarrhea, especially at high doses. If this happens, reduce the dose and work up slowly. The protocol is to take 1 capsule each morning with breakfast for the first week. Add a second capsule with lunch thereafter. If desired a third capsule can be taken with dinner after the third week. If undesired effects occur cut back or eliminate all together. Many people do well on one a day. A lower dose of Galantamind may be needed if used along with antidepressants such as paroxetine (Paxil®), fluoxetine (Prozac®), amitriptyline (Elavil®) or fluvoxamine (Luvox®) and other medications such as ketoconazole, quinidine, erythromycin or cimetidine. These medications may slow the elimination of Galantamind from the body. Anticholinergics, such as antihistamines or drugs used for urinary problems, may reverse the effects of Galantamind.


Take 1 capsule up to 3 times daily with meals.


Studies on Galantamine In Alzheimer’s Disease

Cochrane Database Syst Rev 2002;( 3):CD001747
Galantamine for Alzheimer’s disease (Cochrane Review).

Olin J, Schneider L. Adult and Geriatric Treatment and Preventative Interventions Branch, National Institute of Mental Health, NIMH, Room 7160, MSC 9635, 6001 Executive Blvd., Bethesda, Maryland, USA, 20892-9635.

BACKGROUND: Galantamine (also called galanthamine, marketed by Janssen as Reminyl) was originally isolated from several plants, including daffodil bulbs, but is now synthesized. Galantamine is a specific, competitive, and reversible acetylcholinesterase inhibitor. It is also an allosteric modulator at nicotinic cholinergic receptor sites potentiating cholinergic nicotinic neurotransmission. A small number of early studies showed mild cognitive and global benefits for patients with Alzheimer’s disease (AD), and recently several multicentre clinical trials have been published with positive findings. Galantamine has received regulatory approval in 29 counties: Argentina, Australia, Canada, Czechia, the European Union (except for The Netherlands), Iceland, Korea, Mexico, Norway, Poland, Singapore, South Africa, Switzerland, Thailand, and the United States. OBJECTIVES: The objective of this overview is to assess the clinical effects of galantamine in patients with probable AD, and to investigate potential moderators of an effect. SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 15 May 2002 using the terms galantamine and Reminyl. Published reviews were inspected for further sources. Additional information was collected from an unpublished investigational brochure for galantamine. SELECTION CRITERIA: Trials selected were randomized, double-blind, parallel-group, unconfounded comparisons of galantamine with placebo for a treatment duration of greater than 4 weeks for people with AD. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers and pooled where appropriate and possible. The pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Intention-to-treat and observed cases data were both reported, if the data were available. ~bullet~Outcomes of interest include the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), clinical global impression of change (CIBIC-plus or CGIC), Alzheimer’s Disease Cooperative Study Activities of Daily Living Scale (ADCS-ADL), Disability Assessment for Dementia scale (DAD) and Neuropsychiatric Inventory (NPI). ~bullet~Potential moderating variables of a treatment effect included trial duration and dose. MAIN RESULTS: Seven trials were identified that met criteria for entry, with six being Phase II or III industry-sponsored multicentre trials. Two were of 12 weeks duration; one of 13 weeks, one of 5 months; one of 29 weeks; and two of 6 months duration. Trials of 5 months or more were aggregated together in the analyses as ‘6 months.’ Overall, galantamine showed significant treatment effects at daily doses of 16-32 mg for trials of 3- to 6-months duration. For global ratings, trials of 3 months duration with doses of 24-32mg/d (Odds Ratio (OR) 2.3; 95%CI 1.3 - 3.9) and 36mg/d (OR 3.4; 95%CI 1.2 - 9.5) were statistically significant in favour of treatment. For trials of 6 months duration (5-months to 29 weeks), only doses of 8mg/d failed to be associated with statistically significant benefit (16mg: OR 2.25; 95% CI 1.6 - 3.3; 24mg: OR 2.0; 95%CI 1.5 -2.5; 32mg: OR 1.9; 95%CI 1.4 - 2.5). For cognitive function over 6 months duration: at 16mg/d, improvements measured -3.3 points (k=1; 95%CI -4.4 - -2.1) on weighted mean difference on the ADAS-Cog scale; -3.5 points at 24mg/d (k=3; 95%CI -4.3 - -2.8), and -4.0 points at 32mg/d (k=2; 95%CI -5.0 - -3.0). The two 3-month trials with ADAS-Cog data also showed statistically significant improvement. Both observed cases (WMD 3.8; 95%CI 0.3 - 7.3) and intention-to-treat analyses using the Disability Assessment of Dementia scale gave statistically significant results in favour of treatment for daily doses of 32mg for 6 months duration (as did the single 3-month trial of 24-32mg/d treatment that used this scale). The small number of trials available for analysis, however, limited the power of subgroup analyses to detect differences. Galantamine consistently failed to show statistically significant treatment effects at doses of 8mg/day. Galantamine’s adverse effects appear similar to those of other cholinesterase inhibitors, in that it tends to produce gastrointestinal symptoms acutely and with dosage increases. Overall, participants treated with galantamine at all doses for 3 months were more likely to discontinue that were those given placebo. Participants treated with galantamine at doses of 24-32 mg/d for 6 months were more likely to discontinue in most trials than were those treated with lower doses or placebo, with 32mg/d being associated with significantly higher withdrawal rates than was 24mg/d. However, in the one trial with a slower rate of titration the discontinuation rate was not significantly greater than placebo for the 16 mg/day dose. REVIEWER’S CONCLUSIONS: Patients in these trials were similar to those seen in earlier anti dementia AD trials, and consisted predominantly of mildly to moderately impaired outpatients. Galantamine’s effect on more severely impaired people has not yet been assessed. Never the less, this review shows consistent positive effects for galantamine for trials of 3 months, 5 months and 6 months duration. In addition, although there was not a statistically significant dose-response effect, benefits associated with doses above 8mg/d were, for the most part, consistently statistically significant. There is therefore evidence for efficacy of galantamine on global ratings, cognitive tests, assessments of ADLs and behaviour. This magnitude for the cognitive effect is similar to that associated with other cholinesterase inhibitors including donepezil, rivastigmine, and tacrine. Galantamine’s safety profile is similar to that of other cholinesterase inhibitors with regard to cholinergically mediated gastrointestinal symptoms. No information is available on adverse events that occurred less than 5% of the time. It appears that doses of 16 mg/d were best tolerated in the single trial where medication was titrated over 4-week periods, and because this dose showed statistically indistinguishable efficacy with higher doses, it is probably preferable initially. Longer-term use of galantamine has not been assessed in a controlled fashion.

Lancet 2002 Apr 13;359(9314):1283-90
Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: a randomised trial.

Erkinjuntti T, Kurz A, Gauthier S, Bullock R, Lilienfeld S, Venkata Damaraju C. Department of Clinical Neurosciences, Helsinki University Central Hospital, Helsinki, Finland

Background Vascular dementia is the second commonest form of dementia, and vascular factors contribute to the development of dementia in many patients with Alzheimer’s disease. Galantamine amplifies the acetylcholine response by inhibiting acetylcholinesterase and modulating nicotinic receptors. It has shown broad, sustained benefits in patients with Alzheimer’s disease. We investigated the effects of galantamine in patients with a diagnosis of probable vascular dementia or Alzheimer’s disease combined with cerebrovascular disease.Methods Eligible patients were randomly assigned galantamine 24 mg/day (n=396) or placebo (n=196) in a multicentre, double-blind, 6-month trial. Primary endpoints were cognition (Alzheimer’s disease assessment scale, cognitive subscale [ADAS-cog]) and global functioning (clinician’s interview-based impression of change plus caregiver input [CIBIC-plus]). Secondary endpoints included assessments of activities of daily living and behavioural symptoms. Patients were monitored for adverse events. Analyses were on the basis of observed case or last observation carried forward.Findings Galantamine showed greater efficacy than placebo on ADAS-cog (galantamine change -1 small middle dot7 [SE 0 small middle dot4] vs placebo 1 small middle dot0 [0 small middle dot5]; treatment effect 2 small middle dot7 points; p<0 small middle dot0001) and CIBIC-plus (213 [74%] vs 95 [59%] patients remained stable or improved, p=0 small middle dot001). Activities of daily living and behavioural symptoms were also significantly improved compared with placebo (p=0 small middle dot002 and p=0 small middle dot016, respectively). Galantamine was well tolerated. Interpretation: Galantamine showed a therapeutic effect on all key areas of cognitive and non-cognitive abilities in this group of dementia patients.

Int J Geriatr Psychiatry 2001 Sep;16(9):852-7
Galantamine: a randomized, double-blind, dose comparison in patients with Alzheimer’s disease.

Wilkinson D, Murray J. Old Age Psychiatry, Thornhill Research Unit, Moorgreen Hospital, Southampton, UK.

OBJECTIVES: To investigate whether Galantamine significantly improves the core symptoms of Alzheimer’s disease (AD). BACKGROUND: Galantamine is a reversible, competitive, selective inhibitor of acetylcholinesterase (AChE) that also allosterically modulates nicotinic acetylcholine receptors. This dual mechanism of action provided the rationale for a phase II trial of galantamine in AD. METHOD: A multicentre, randomized, parallel, double-blind, placebo-controlled trial was carried out to evaluate the efficacy and tolerability of galantamine 18, 24 and 36 mg/day administered for 3 months in 285 patients with mild-to-moderate probable AD. The primary outcome measure was the Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog); secondary outcome measures were the Clinical Global Impression of Change (CGIC) and the Progressive Deterioration Scale (PDS). RESULTS: Patients treated with galantamine 24 mg/day had a significantly better outcome than placebo on ADAS-cog; the treatment difference was 3 points on the intention-to-treat (ITT) analysis ( p = 0.01) and 4.2 points on per protocol analysis ( p = 0.001). Per protocol analysis showed that galantamine had a significantly better outcome than placebo on PDS ( 24-mg/day dose, p < 0.05) and CGIC (36-mg/day dose, p < 0.05). Galantamine was well tolerated at the lower doses of 18 and 24 mg/day where it produced mild, transient effects typical of cholinomimetic agents. CONCLUSION: This study shows that, relative to placebo, galantamine significantly improves the core symptoms of Alzheimer’s disease.

BMJ 2000 Dec 9;321(7274):1445-9
Efficacy and safety of galantamine in patients with mild to moderate Alzheimer’s disease: multicentre randomised controlled trial. Galantamine International-1 Study Group.

Wilcock GK, Lilienfeld S, Gaens E. Department of Care of the Elderly, Frenchay Hospital, University of Bristol, Bristol BS16 1LE.

OBJECTIVE: To evaluate the efficacy and safety of galantamine in the treatment of Alzheimer’s disease. DESIGN: Randomised, double blind, parallel group, placebo controlled trial. SETTING: 86 outpatient clinics in Europe and Canada. PARTICIPANTS: 653 patients with mild to moderate Alzheimer’s disease. INTERVENTION: Patients randomly assigned to galantamine had their daily dose escalated over three to four weeks to maintenance doses of 24 or 32 mg. MAIN OUTCOME MEASURES: Scores on the 11 item cognitive subscale of the Alzheimer’s disease assessment scale, the clinician’s interview based impression of change plus caregiver input, and the disability assessment for dementia scale. The effect of apolipoprotein E4 genotype on reponse to treatment was also assessed. RESULTS: At six months, patients who received galantamine had a significantly better outcome on the 11 item cognitive subscale of the Alzheimer’s disease assessment scale than patients in the placebo group (mean treatment effect 2.9 points for lower dose and 3.1 for higher dose, intention to treat analysis, P<0.001 for both doses). Galantamine was more effective than placebo on the clinician’s interview based impression of change plus caregiver input (P<0.05 for both doses v placebo). At six months, patients in the higher dose galantamine group had significantly better scores on the disability assessment for dementia scale than patients in the placebo group (mean treatment effect 3.4 points, P<0.05). Apolipoprotein E genotype had no effect on the efficacy of galantamine. 80% (525) of patients completed the study. CONCLUSION: Galantamine is effective and well tolerated in Alzheimer’s disease. As galantamine slowed the decline of functional ability as well as cognition, its effects are likely to be clinically relevant.

Neurology 2000 Jun 27;54(12):2269-76
A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group.

Tariot PN, Solomon PR, Morris JC, Kershaw P, Lilienfeld S, Ding C. Department of Psychiatry, University of Rochester Medical Center, NY 14620, USA.

OBJECTIVE: To investigate the efficacy and tolerability of galantamine, using a slow dose escalation schedule of up to 8 weeks, in 978 patients with mild to moderate AD. METHODS: A 5-month multicenter, placebo-controlled, double-blind trial. Following a 4-week placebo run-in, patients were randomized to one of four treatment arms: placebo or galantamine escalated to final maintenance doses of 8, 16, or 24 mg/day. Outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog), the Clinician’s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the AD Cooperative Study Activities of Daily Living inventory, and the Neuropsychiatric Inventory. Standard safety evaluations and adverse event monitoring were carried out. RESULTS: After 5 months, the galantamine-placebo differences on ADAS-cog were 3.3 points for the 16 mg/day group and 3.6 points for the 24 mg/day group (p < 0.001 versus placebo, both doses). Compared with placebo, the galantamine 16- and 24-mg/day groups also had a significantly better outcome on CIBIC-plus, activities of daily living, and behavioral symptoms. Treatment discontinuations due to adverse events were low in all galantamine groups (6 to 10%) and comparable with the discontinuation rate in the placebo group (7%). The incidence of adverse events in the galantamine groups, notably gastrointestinal symptoms, was low and most adverse events were mild. CONCLUSIONS: Galantamine at 16 and 24 mg/day significantly benefits the cognitive, functional, and behavioral symptoms of AD as compared with placebo. Slow dose escalation appears to enhance the tolerability of galantamine, minimizing the incidence and severity of adverse events.

Neurology 2000 Jun 27;54(12):2261-8
Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group.

Raskind MA, Peskind ER, Wessel T, Yuan W. Veteran Affairs Puget Sound Health Care System and the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle 98108, USA.

BACKGROUND: Galantamine is a reversible, competitive cholinesterase inhibitor that also allosterically modulates nicotinic acetylcholine receptors. These mechanisms of action provided the rationale for a therapeutic trial of galantamine in AD. METHODS: A 6-month, multicenter, double-blind trial was undertaken in 636 patients with mild to moderate AD. Patients were randomly assigned to placebo or galantamine and escalated to maintenance doses of 24 or 32 mg/d. Eligible patients then entered a 6-month, open-label study of the 24 mg/d dose. Primary efficacy measures were the 11-item AD Assessment Scale cognitive subscale (ADAS-cog/11) and the Clinician’s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). The Disability Assessment for Dementia (DAD) scale was a secondary efficacy variable. RESULTS: Galantamine significantly improved cognitive function relative to placebo; the treatment effects were 3.9 points (lower dose) and 3.8 points (higher dose) on the ADAS-cog/11 scale at month 6 (p < 0.001 in both cases). Both doses of galantamine produced a better outcome on CIBIC-plus than placebo (p < 0.05). Therapeutic response to galantamine was not affected by APOE genotype. At 12 months, mean ADAS-cog/11 and DAD scores had not significantly changed from baseline for patients who received galantamine 24 mg/d throughout the 12 months. The most common adverse events, which were predominantly gastrointestinal, decreased in frequency during long-term treatment. There was no evidence of hepatotoxicity. CONCLUSIONS: Galantamine is effective and safe in AD. At 6 months, galantamine significantly improved cognition and global function. Moreover, cognitive and daily functions were maintained for 12 months with the 24 mg/d dose.

Expert Opin Pharmacother 2001 Dec;2(12):2027-49
Current status and new developments with galantamine in the treatment of Alzheimer’s disease.

Tariot P. Department of Psychiatry and Program in Neurobehavioural Therapeutics, Monroe Community Hospital, 435 East Henrietta Road, Rochester, NY 14620, USA.

Galantamine is a newly available cholinergic drug that offsets reductions in central cholinergic neurotransmission in Alzheimer’s disease (AD) by specifically and reversibly inhibiting acetylcholinesterase (AChE) and by allosterically modulating nicotinic cholinergic receptors. The clinical impact of this latter mechanism of action has not been fully elucidated. Galantamine has favorable pharmacokinetic features including linear elimination kinetics, a relatively short half-life and high oral bioavailability. The efficacy of galantamine has been studied in an extensive clinical development program. During randomised, double-blind, placebo-controlled trials of up to 6 months’ duration, galantamine 16 and 24 mg/day consistently produced a broad spectrum of beneficial effects on cognitive and non-cognitive AD symptoms. Patients’ cognition, global function and abilities to perform both instrumental and basic activities of daily living were maintained, the emergence of behavioral symptoms was postponed and apparent reductions in caregiver burden were seen. In long-term studies (12 months), galantamine maintained cognitive and functional abilities at or near baseline levels for at least 12 months. Again, these benefits were associated with decreases in caregiver burden. The incidence of adverse events, which are typically mild or moderate in severity, is generally low with galantamine. Cholinergically mediated adverse events affecting mainly the gastrointestinal system can be minimized using the recommended slow dose-escalation regimen. Galantamine may therefore help reduce the overall burden and cost involved in caring for AD patients. Being approved for the treatment of mild-to-moderately severe AD in both the US and in Europe, with trials of its efficacy in other dementia types already yielding positive results, galantamine ranks as a first-line therapy for dementia.

Drugs 2000 Nov;60(5):1095-122
Galantamine: a review of its use in Alzheimer’s disease.

Scott LJ, Goa KL. Adis International Limited, Auckland, New Zealand.

Currently, acetylcholinesterase (AChE) inhibitors are the most promising class of drugs for the treatment of Alzheimer’s disease (AD). Galantamine is a reversible, competitive, tertiary alkaloid AChE inhibitor. The drug is selective for AChE rather than butyrylcholinesterase. In addition to inhibition of AChE galantamine interacts allosterically with nicotinic acetylcholine receptors to potentiate the action of agonists at these receptors. Recipients of galantamine 16 or 24 mg/day achieved significant improvements in cognitive and global symptoms relative to placebo recipients in large (n = 285 to 978 patients with mild to moderate AD) well-designed trials of 3 to 6 months’ duration. Galantamine also improved activities of daily living in these patients and significantly reduced the requirement for caregiver assistance with activities of daily living. Moreover, galantamine recipients achieved significantly better outcomes on behavioral symptoms than placebo recipients. In a long-term study (12 months), galantamine 24 mg/day slowed the progression of symptoms of the disease and maintained cognitive function and activities of daily living in patients with mild to moderate AD. Galantamine was generally well tolerated with the majority of adverse events being mild to moderate in intensity and transient. Predictably, adverse events were cholinergic in nature and generally related to the gastrointestinal system. These effects were reduced in patients receiving the recommended dose escalation regimen. Galantamine had no clinically relevant effects on vital signs, hematological or biochemical laboratory parameters and, importantly, there were no reports of hepatotoxicity. The incidence of serious adverse events was similar between galantamine (8 to 32 mg/day) and placebo groups (6 to 16% of patients across all treatment groups). CONCLUSIONS: Galantamine is an effective well tolerated symptomatic treatment for AD which improves cognition, function and activities of daily living in the short term (up to 6 months) in patients with mild to moderate AD. In addition, it delays the development of behavioral disturbances and psychiatric symptoms, and reduces caregiver burden (as measured by caregiver time). In the long term (up to 1 year), galantamine maintains cognition and activities of daily living. Adverse events associated with galantamine are mainly cholinergic, usually mild to moderate in intensity and transient. Galantamine has been evaluated in several large well-designed studies & given the relative lack of established treatment options; it may be considered one of the first-line pharmacological treatments in patients with mild to moderate AD.

Dement Geriatr Cogn Disord 2000 Sep;11 Suppl 1:28-34
Galantamine: therapeutic effects beyond cognition.

Blesa R. Neurology Department, Hospital Clinic, University of Barcelona, Spain.

Decline in cognitive function, especially memory, is the core feature of Alzheimer’s disease (AD). However, other characteristic aspects of the disease are also important. These include patients’ activities of daily living (ADL), including quality of sleep, behavioral disturbances and the impact of the disease on the caregiver. Therefore, increasing attention is being paid to clinically meaningful outcome measures, such as the Disability Assessment for Dementia (DAD) scale, the Neuropsychiatric Inventory (NPI), caregiver time and the Pittsburgh Sleep Quality Index (PSQI). Galantamine is a new treatment for AD that combines modulation of nicotinic receptors with inhibition of acetylcholinesterase. The present review outlines the positive and sustained effects of this agent on patients’ behaviour and daily functioning as well as on caregiver time. In studies of up to 5 months’ duration, galantamine-treated patients had a significantly better outcome on ADL than placebo-treated patients, and after 12 months of treatment with galantamine, patients’ functional ability was preserved. Galantamine also significantly benefits behavioral disturbances in patients with AD. These functional and behavioral benefits are associated with a decrease in the burden on caregivers, as indicated by a reduction, relative to placebo, in the time spent supervising and assisting patients. These clinical benefits are not offset by disruption of patients’ sleep, as has been reported with other cholinergic treatments.

[Above studies from Medline]

Galantamine In Vascular Dementia

Lancet 2002 Apr 13;359(9314):1283-90
Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: a randomised trial

Erkinjuntti T, Kurz A, Gauthier S, Bullock R, Lilienfeld S, Damaraju CV. Department of Clinical Neurosciences, Helsinki University Central Hospital, Helsinki, Finland.

BACKGROUND: Vascular dementia is the second commonest form of dementia, and vascular factors contribute to the development of dementia in many patients with Alzheimer’s disease. Galantamine amplifies the acetylcholine response by inhibiting acetylcholinesterase and modulating nicotinic receptors. It has shown broad, sustained benefits in patients with Alzheimer’s disease. We investigated the effects of galantamine in patients with a diagnosis of probable vascular dementia or Alzheimer’s disease combined with cerebrovascular disease. METHODS: Eligible patients were randomly assigned galantamine 24 mg/day (n=396) or placebo (n=196) in a multicentre, double-blind, 6-month trial. Primary endpoints were cognition (Alzheimer’s disease assessment scale, cognitive subscale [ADAS-cog]) and global functioning (clinician’s interview-based impression of change plus caregiver input [CIBIC-plus]). Secondary endpoints included assessments of activities of daily living and behavioural symptoms. Patients were monitored for adverse events. Analyses were on the basis of observed case or last observation carried forward. FINDINGS: Galantamine showed greater efficacy than placebo on ADAS-cog (galantamine change -1.7 [SE 0.4] vs placebo 1.0 [0.5]; treatment effect 2.7 points; p<0.0001) and CIBIC-plus (213 [74%] vs 95 [59%] patients remained stable or improved, p=0.0001). Activities of daily living and behavioural symptoms were also significantly improved compared with placebo (p=0.002 and p=0.016, respectively). Galantamine was well tolerated. INTERPRETATION: Galantamine showed a therapeutic effect on all key areas of cognitive and non-cognitive abilities in this group of dementia patients.

Lancet 2002 Apr 13;359(9314):1283-90
Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: a randomised trial.

Erkinjuntti T, Kurz A, Gauthier S, Bullock R, Lilienfeld S, Damaraju CV. Department of Clinical Neurosciences, Helsinki University Central Hospital, Helsinki, Finland.

BACKGROUND: Vascular dementia is the second commonest form of dementia, and vascular factors contribute to the development of dementia in many patients with Alzheimer’s disease. Galantamine amplifies the acetylcholine response by inhibiting acetylcholinesterase and modulating nicotinic receptors. It has shown broad, sustained benefits in patients with Alzheimer’s disease. We investigated the effects of galantamine in patients with a diagnosis of probable vascular dementia or Alzheimer’s disease combined with cerebrovascular disease. METHODS: Eligible patients were randomly assigned galantamine 24 mg/day (n=396) or placebo (n=196) in a multicentre, double-blind, 6-month trial. Primary endpoints were cognition (Alzheimer’s disease assessment scale, cognitive subscale [ADAS-cog]) and global functioning (clinician’s interview-based impression of change plus caregiver input [CIBIC-plus]). Secondary endpoints included assessments of activities of daily living and behavioural symptoms. Patients were monitored for adverse events. Analyses were on the basis of observed case or last observation carried forward. FINDINGS: Galantamine showed greater efficacy than placebo on ADAS-cog (galantamine change -1.7 [SE 0.4] vs placebo 1.0 [0.5]; treatment effect 2.7 points; p<0.0001) and CIBIC-plus (213 [74%] vs 95 [59%] patients remained stable or improved, p=0.0001). Activities of daily living and behavioural symptoms were also significantly improved compared with placebo (p=0.002 and p=0.016, respectively). Galantamine was well tolerated. INTERPRETATION: Galantamine showed a therapeutic effect on all key areas of cognitive and non-cognitive abilities in this group of dementia patients.

[Above studies from Medline]


“You see, I don’t want to do good things, I want to do great things.” ~Alexander Joseph Luthor

I know Lewd Ferrigno personally.

Huperzine A

Huperzine A is an extract of the Chinese club moss Huperzia serrata. In China it is called Qian Ceng Ta and has been used for centuries.

Huperzine A is a memory and learning enhancing substance especially useful for early or moderate stage Alzheimer’s Disease.
One of the most important neurotransmitters in the brain is acetylcholine. Many studies have linked high levels of this chemical to enhanced learning and memory abilities. Acetylcholine, like other neurotransmitters, is produced in the gap (synapse) between nerve cells. It is then rapidly broken down by the enzyme acetylcholinesterase. Huperzine A blocks acetylcholinesterase and therefore builds up the amount of Acetylcholine in the synapse.
It is similar to but more potent than prescription drugs tacrine and donepezil.
Controlled, double-blind studies have been performed in China which have yielded positive results in quality of life and ability to retrieve memories in patients with various dementias.
It may also be useful for older people who are beginning to become forgetful. If experiments with choline are any indication it may also be useful for students or others whose memory and learning ability are important. In fact, taken just before studying or a test, it may have a strong mental boosting effect.
It is also believed that Huperzine A has neuroprotective properties against various toxins. For example, it protects against glutamate excitotoxicity.

Huperzine A is non-toxic even at doses 100 times the therapeutic dose. Some cases of dizziness have emerged and the potential for nausea or excessive salivation is possible. Long term use is thought to potentially raise acetylcholine levels to an unacceptably high level. It is probably better to use this intermittently, as for studying or tests. Alzheimer’s patients may use it long term with a doctor’s supervision. The usual precautions in pregnant or nursing women apply.
Take 50 mcg 1-4 times daily.

[Above info from]

Huperzine-A: Natural Club Moss Extract Shows Promise for Treating Alzheimer’s, Enhancing Memory and Alertness

By Jim English

Alzheimer’s Disease (AD) is a progressive degenerative disease that most commonly appears after the age of 50. Currently, Alzheimer’s afflicts approximately 40% of all individuals over the age of 85, for a total of 4 million people in the U.S. alone. When symptoms occur before the age of 65 the disease is designated Presenile Dementia of the Alzheimer’s Type (PDAT). When symptoms occur after age 65 the syndrome is referred to as Senile Dementia of the Alzheimer’s Type (SDAT). Symptoms include a gradual yet inexorable loss of memory, mental performance, communication skills, abstract thinking and personality. Ultimately, Alzheimer’s ends in the death of the patient, with a mean life expectancy of 8 years.

As well as being a profound personal tragedy for afflicted individuals and their loved ones, the financial costs of caring for victims of the disease exceed $80 billion per year. The current trend towards longer life expectancy, combined with the increased incidence of senile dementia with age, means that cases of Alzheimer’s increase alarmingly as the median age of the population grows, underscoring the urgency for finding an effective treatment for this disorder.

Huperzine-A is a new supplement derived from an ancient traditional Chinese herbal medicine that offers hope to those suffering from Alzheimer’s disease and other age-related mental conditions. In addition to benefiting patients suffering from Alzheimer’s, Huperzine’s memory-enhancing properties suggest that it may be an effective agent for improving memory and learning in healthy humans as well.

Cholinergic Dysfunction in Alzheimer’s
Alzheimer’s is characterized by the destruction of nerve cells in several key areas of the brain devoted to mental functions. This results in tangles of nerve fibers and plaque formation of an abnormal, insoluble protein called amyloid. While there is a general reduction in the concentration of all neurotransmitting substances, a marked clinical feature of the disease is a dramatic decrease in the neurotransmitter acetylcholine. Acetyl-choline is a vital neurotransmitter with a fundamental role in memory. It is also necessary for proper intracellular communication between nerve cells. Research has shown that levels of acetylcholine are deficient in the brains of patients with Alzheimer’s disease.
Biopsy and postmortem studies have shown that there is a substantial loss of presynaptic cholinergic neurons in brains of patients with Alzheimer’s. What little acetylcholine that is still produced in the patient’s brain is quickly broken down by the brain enzyme, acetylcholinesterase (AchE), leading to a shortage of the neurotransmitter and contributing to the patient’s loss of memory and other cognitive functions.

Prescription Alzheimer’s Drugs
Two drugs are currently approved for use in the U.S. to treat Alzheimer’s—Tacrine™ and Donepezil hydrochloride (Aricept™). Both drugs are moderately effective cholinesterase inhibitors that work by interfering with the actions of AChE. Since acetylcholine is normally degraded and recycled by acetylcholinesterase, this approach counteracts any further reduction of already low levels of acetylcholine.
By inhibiting the actions of AChE it is hoped that the small amounts of acetylcholine still being produced will persist longer within the synaptic cleft and lead to improvements in memory and cognitive abilities. While both drugs are effective cholinesterase inhibitors, they suffer from a number of drawbacks. First, they are available only by prescription; second, they are expensive, costing between $100-$240 per month; and third, both drugs can cause debilitating side effects including liver toxicity (Tacrine), and nausea and diarrhea (Donepezil).

Huperzine A: A Safe Alternative
Huperzine A is a natural compound derived from an ancient Chinese remedy, Qian Ceng Ta. This traditional herbal medicine was prepared from Huperzia serrata, a clubmoss that grows on the ground in damp forests and rock crevices. Brewed as an herbal tea, Qian Ceng Ta has been used in China to treat fever, inflammation, and irregular menstruation, and has been used as a diuretic. In the late 1980’s, researchers in China discovered that a purified alkaloid extracted from Huperzia, Huperzine A, was a potent, reversible inhibitor of acetylcholin-esterase (AChE). Huperzine A readily crosses the blood-brain barrier to prevent acetylcholinesterase (AchE) from destroying acetylcholine.

Molecular Monkey Wrench
A study at the Weizmann Institute in Israel uncovered how Huperzine A (Hup-A) works to block acetylcholinesterase.2 Scientists had previously learned that AchE inhibitors such as tacrine and donepezil worked by sliding into the AChE molecule to “jam up” its molecular machinery and impair its ability to degrade acetylcholine. By imaging a 3-dimensional structure of the AChE molecule, the researchers were able to peer into the complex folded protein structure to discover a deep chasm, called the active-site gorge. The scientists determined that the active-site gorge acts as a guide to funnel acetylcholine into the interior of the enzyme where it is cut apart prior to recycling. This study revealed that Huperzine A has a strong specificity for AChE, and is exceptionally well suited to its new role, fitting into the active sites of acetylcholinesterase much like a key slipping into a lock. “Hup-A appears to bind more tightly and specifically to acetylcholinesterase than the other AChE inhibitors,” crystallographer Prof. Joel Sussman, one of the authors of the study said. “It is as if this natural substance were ingeniously designed to fit into the exact spot in AChE where it will do the most good.”

Clinical Studies
Hup-A has undergone double blind, placebo-controlled clinical trials in China in patients suffering from various memory disorders, including AD. In fact, it is estimated that in the past few years 100,000 people have been treated in China with Hup-A. Researchers in China claim that it helps normal elderly with memory problems and people with AD.
Double-blind, placebo-controlled clinical trials in China have demonstrated that patients suffering from Alzheimer’s and various other memory disorders gain significant benefit, both in terms of memory and life quality. Xu et al. conducted a placebo-controlled, double-blind study in which subjects with AD were given 200 mcg/day Hup-A or placebo for 8 weeks. Statistically significant improvement was achieved in 58% of the treated group with respect to cognitive function and their ability to retrieve past memories.

In one study, Chinese researchers of the Department of Pharmacology, Zhejiang Academy of Medical Sciences, Hangzhou, China, examined the effects of Hup-A on six volunteers. They concluded that Hup-A had a high rate of absorption and distribution in the body, and was without adverse side effects.

A second study conducted by researchers at Zhejiang Medical University, focused on the efficacy of Hup-A on memory, cognition, and behavior in Alzheimer’s disease. This multicenter, double-blind, placebo controlled study found that about 58% (29/50) of patients treated with Hup A showed improvements in their memory, cognition, and behavioral functions. No severe side effects were found. All patients were evaluated with Wechsler memory scale, Hasegawa dementia scale, mini-mental state examination scale, activity of daily living scale, treatment emergency symptom scale, and measured with BP, HR, ECG, EEG, ALT, AKP, BUN, Cr, Hb, WBC, and urine routine. Their conclusion was that “Hup-A is a promising drug for symptomatic treatment of
Alzheimer’s disease.”

In the U.S., a recent paper by noted neurologist, Alan A. Mazurek, M.D., reported on the results of an office-based trial studying the safety and efficacy of Hup-A as a treatment for Alzheimer’s disease. Mazurek evaluated the safety and efficacy of Hup-A in an open-label trial involving 29 patients with mild to moderate AD.

Twenty-two patients (75.9%) completed the three-month study. Only two patients reported adverse effects, one being an apparently unrelated hemorrhagic infarct that resolved without treatment. No gastrointestinal side effects, nausea, diarrhea, cardiac effects or headache were reported. Status Examinations’ (SMMSE) improvement of one point or greater was seen at one, two and three months. Mazurek reported that improvements appeared to be dose related, with those on the higher dosages exhibiting the greatest improvement. Wrote Mazurek, “Hup-erzine A appears to be safe, well tolerated, and effective in the symptomatic treatment of AD.”

Other Benefits
In addition to its activity as an AChE inhibitor, ongoing research suggests that Hup-A has a wider role to play in supporting neuroprotective functions. Researchers recently discovered that Hup-A inhibits glutamate-induced cytotoxicity, protecting neonatal hippocampal and cerebellar neuronal cells in culture from death caused by the amino acid glutamate. In addition to protecting from glutamate-induced cytotoxicity, researchers were also surprised to learn that Huperzine A promotes new dendrite outgrowth of neuronal cultures.

Potential Protection for Chemical Warfare
Researchers at the Walter Reed Army Institute of Research in Washington D.C. are conducting studies into Huperzine’s potential role as a pretreatment drug to protect against chemical warfare nerve agent poisoning. In one study, Huperzine A was found to be twice as effective in protecting mice against the lethal effects of the nerve agent soman when compared to physostigmine. Huperzine A’s effects lasted for six hours compared to only 90 minutes for physostigmine, providing further evidence for the slow clearance of Huperzine from the body.

Huperzine A has a wide margin of safety. Toxicology studies show Huperzine A to be non-toxic even when administered at 50-100 times the human therapeutic dose! The extract is active for 6 hours at a dose of 2 µg/kg with no remarkable side effects.

Huperzine A appears to be a safe memory supplement. Clinical research has shown that Huperzine A is superior to other cholinesterase inhibitors such as tacrine and donepezil. Huperzine A is rapidly absorbed when taken orally, and possesses a very slow rate of dissociation from the enzyme and a longer duration of action. Studies in rodents show that AChE remains inhibited by 33% after 6 hours.

Huperzine A has been shown to be effective in inhibiting the actions of AChE to increase acetylcholine concentrations and alleviate some of the symptoms associated with acetylcholine deficiencies. Significant effects have been noted in patients both in terms of their life quality and their ability to retrieve past memories. In view of the fact that Huperzia serrata was used for many years in Chinese folklore medicine, and in accord with the Dietary Supplement Health & Education Act of 1994 (DSHEA) in this country, it has been possible to introduce Hup-A into the US market as a dietary supplement. These findings suggest that Hup-A not only protect from the actions of Alzheimer’s and senile memory deficits, but also provides a unique and exciting supplement for supporting memory in the healthy aging human as well. Accordingly, Huperzine A is currently available as an over the counter “nutriceutical” for those individuals looking for support for memory.

[Above info from]

For Young and Old Alike Huperzine A: Brain Booster Research in China Shows Benefits in Adolescents As Well As Alzheimer’s Patients

Take acetylcholinesterase - please. It’s one of the more unloved substances in the human body, because it acts as a kind of molecular butcher, cleaving other molecules in half with grim efficiency. But at least it’s highly selective, always seeking and destroying only the acetylcholine molecule, which it splits into acetate and choline. Such specificity is characteristic of all enzymes - proteins that are designed to carry out just one task, through their catalytic activity.
Acetylcholine, as most readers probably know, is a versatile neurotransmitter, a messenger molecule that acts throughout the central and peripheral nervous systems to mediate a host of vital functions, including many related to cognition and memory. It is a molecule devoutly to be desired in ample quantities, not only so we can keep all our marbles, but also so they can stay bright and shiny for the endlessly varied game of life.
Why then, did Mother Nature unleash an enzymatic assassin to keep cutting the poor acetylcholine molecules in half? Because - and this is as true of biomolecules as anything else - too much of a good thing is a bad thing (think glucose and diabetes, e.g.). There must always be checks and balances and feedback mechanisms to ensure that there is just enough of what we need, neither too little nor too much. And so there are “good” molecules that we need for optimal health, and “bad” molecules (which aren’t really bad, because they serve a necessary purpose) that keep the good ones from creating havoc through overabundance.
Furthermore, in a chemical analogue to military electronic countermeasures technology, there is a second tier of “good” molecules that serve to jam the actions of the bad ones, when necessary, by inhibiting their ability to perform their assigned functions. One such is huperzine A, an acetylcholinesterase inhibitor - bad for acetylcholinesterase and therefore good for acetylcholine. And, like Chinese boxes, there are yet other molecules that inhibit the inhibitors …
In this cats-and-mice game, there is, as always in living organisms, a delicate balance to be maintained. And, as always, the balance can get skewed as we age, for some reasons that we understand and many more that we don’t. In any case, if acetylcholinesterase gains the upper hand and unduly depletes our stores of acetylcholine, really bad things can happen, such as Alzheimer’s disease - not that there is a clear cause and effect there (few things, including Alzheimer’s, are that simple), but there is a strong correlation that can’t be ignored.

In the August 1999 issue of Life Enhancement, we presented evidence that huperzine A (HupA for short), an alkaloid found in the Chinese herb Huperzia serrata, is effective in improving cognitive and memory abilities in humans, including those with Alzheimer’s disease. Now there is more evidence. In China, where HupA is used for treating Alzheimer’s and myasthenia gravis, medical scientists have studied its effects on the mental functions of elderly Alzheimer’s patients.
In a rigorously designed and controlled experiment, 60 patients aged 52 to 80 with impaired faculties were treated with synthetic HupA (200 micrograms twice daily) or placebo for 60 days. They were evaluated with a huge array of both psychological and physiological tests to determine their mental and physical health before and after the treatment - and, in particular, to determine whether it made any difference if the HupA was administered in the form of capsules or tablets.
Based on four of the most important psychological tests, including memory function, the improvement rates in both groups ranged from 43% to 70%; there was no statistically significant difference between the capsule group and the tablet group.
The researchers also set out to observe the action of HupA on the damaging effects of oxygen free radicals in the patients’ plasma and erythrocytes (red blood cells). Biochemical tests showed significant improvement, although not to the reference values for healthy people in the same age group. The authors speculate that long-term treatment with HupA might be required to optimize the results.
The study also reconfirmed the previously demonstrated safety as well as efficacy of HupA. The only side effects noted were mild to moderate nausea and insomnia, again with no difference between the capsule and tablet groups.
When a nutrient that improves mental function in the aged does the same in the young, that’s really interesting. And that is what Chinese researchers found, in a study designed to determine the efficacy of HupA on memory and learning in adolescents. They selected 34 matched pairs of apparently normal junior middle school students whose only significant complaints were of poor memory and difficulty in learning.
The pairing was done in terms of age, sex, memory quotient, and overall psychological health, to ensure that comparisons would be meaningful. Using these criteria, the researchers found no statistically significant baseline differences between the students in the two groups, one of which was to be treated with HupA, the other to receive a placebo.
In a double-blind trial, one member of each pair, chosen randomly, was given 100 micrograms of synthetic HupA twice daily for four weeks, while the other member received the placebo. The students’ memory quotients were measured before and after the trial, and their academic performance in their Chinese, English, and mathematics lessons was monitored as well.
The results: At the end of the study, the HupA group scored significantly better than the control group on standard memory tests described as “accumulation,” “recognition,” “reproduction,” “association,” “tactual [tactile] memory,” and “number of recitation,” but not on tests of “picture memory” or “understanding.” They had also done significantly better in their Chinese and English lessons, but not in math. No side effects of any kind were noted.

[Above info from]

“You see, I don’t want to do good things, I want to do great things.” ~Alexander Joseph Luthor

I know Lewd Ferrigno personally.

Huperzine A Studies

Zhongguo Yao Li Xue Bao 1999 Jul;20(7):601-3
Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students.

Sun QQ, Xu SS, Pan JL, Guo HM, Cao WQ. Xiaoshan Mental Hospital, Zhejiang, China.

AIM: To study the efficacy of huperzine-A capsules (Hup) on memory and learning performance of adolescent students. METHODS: Using double-blind and matched pair method, 34 pairs of junior middle school students complaining of memory inadequacy were divided into two groups by normal psychological health inventory (PHI), similar memory quotient (MQ), same sex and class. The Hup group was administrated orally 2 capsules of Hup (each contains Hup 50 micrograms) b.i.d., and the placebo group was given 2 capsules of placebo (starch and lactose inside) b.i.d. for 4 wk. RESULTS: At the end of trial, the Hup group’s MQ (115 +/- 6) was more than that of the placebo group (104 +/- 9, P < 0.01), and the scores of Chinese language lesson in the Hup group were elevated markedly too. CONCLUSION: The Hup capsules enhance the memory and learning performance of adolescent students.

Zhongguo Yao Li Xue Bao 1999 Jun;20(6):486-90
Huperzine-A in capsules and tablets for treating patients with Alzheimer disease.

Xu SS, Cai ZY, Qu ZW, Yang RM, Cai YL, Wang GQ, Su XQ, Zhong XS, Cheng RY, Xu WA, Li JX, Feng B. Zhejiang Mental Health Institute, Hangzhou, China.

AIM: To compare the efficacy and safety between huperzine-A (Hup) in capsules and tablets for treating patients with Alzheimer disease (AD). METHODS: Using multicenter, prospective, double-blind, double-mimic, parallel, positive controlled and randomized methods, 60 patients meeting with the NINCDS-ARDRA criteria of AD were divided into 2 equal groups. Patients in the capsule group received 4 capsules of Hup (each contains 50 micrograms) and 4 tablets of placebo (lactose and starch inside); while the tablet group received 4 tablets of Hup (each contains 50 micrograms) and 4 capsules of placebo, p.o., twice a day for 60 d. All the patients were evaluated with a lot of related ranting scales, and physiological and laboratory examination. RESULTS: There were significant differences (P < 0.01) on all the psychological evaluations between ‘before’ and ‘after’ the 60-d trial of 2 groups, but there was no significant difference between 2 groups by group t test (P > 0.05). The changes of oxygen free radicals in 2 groups showed marked improvement. No severe side effect besides moderate to mild nausea was found in both groups. CONCLUSION: There is equal efficacy and safety between Hup in capsule and tablet for treating patients with AD, and Hup can reduce the pathological changes of the oxygen free radicals in the plasma and erythrocytes of patients with AD.

Zhongguo Yao Li Xue Bao 1995 Sep;16(5):391-5
Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer’s disease.

Xu SS, Gao ZX, Weng Z, Du ZM, Xu WA, Yang JS, Zhang ML, Tong ZH, Fang YS, Chai XS, et al. Zhejiang Supervision and Detection Station of Drug Abuse, Zhejiang Medical University, Hangzhou, China.

AIM: To evaluate the efficacy and safety of tablet huperzine-A (Hup) in patients with Alzheimer’s disease. METHODS: Using multicenter, prospective, double-blind, parallel, placebo controlled and randomized method, 50 patients were administered orally 0.2 mg (4 tablets) Hup and 53 patients were given po 4 tablets of placebo bid for 8 wk. All patients were evaluated with Wechsler memory scale, Hasegawa dementia scale, mini-mental state examination scale, activity of daily living scale, treatment emergency symptom scale, and measured with BP, HR, ECG, EEG, ALT, AKP, BUN, Cr, Hb, WBC, and urine routine. RESULTS: About 58% (29/50) of patients treated with Hup showed improvements in their memory (P < 0.01), cognitive (P < 0.01), and behavioral (P < 0.01 functions. The efficacy of Hup was better than placebo (36%, 19/53) (P < 0.05). No severe side effect was found. CONCLUSION: Hup is a promising drug for symptomatic treatment of Alzheimer’s disease.

[Studies from Medline]

“You see, I don’t want to do good things, I want to do great things.” ~Alexander Joseph Luthor

I know Lewd Ferrigno personally.



Pyritinol is derived from natural sources. It is two pyridoxine (vitamin B6) molecules linked with sulfur bonds. It has no B6 activity, however.

Pyritinol is one of the oldest nootropic (intelligence enhancing) substances around. It has been used in Europe for many conditions such as organic psychoses, cerebral circulatory disorders, alcoholism, dyslexic factors, behavior and intellect disorders in children and post-cerebral infarction (stroke) states. It is also useful for brain aging, ADD, and learning disabilities associated with retardation.
Pyritinol is a strong antioxidant, superior to DMAE or Piracetam in the brain. It is especially effective against the dangerous hydroxyl radical.
This substance increases brain cell energy by enhancing blood glucose transport through the blood-brain barrier and by increasing brain cells utilization of glucose, the sugar the body burns for energy. In a double-blind, placebo controlled, study of 87 patients with various brain disorders, it was found that they used only about 50% of the normally available glucose. Those taking Pyritinol returned to normal in the glucose uptake and their clinical symptoms similarly improved. Most dementias such as Alzheimer’s, stroke, or drug toxicities are characterized by impaired brain carbohydrate metabolism (BCM.) The degree of impairment corresponds to the severity of symptoms.
A study compared Pyritinol with Hydergine™, (a drug used for Alzheimer’s) and Pyritinol was found to be associated with a continuous and significant improvement in symptoms. Hydergine’s results were more modest and tended to plateau early in the treatment.
In the immune system, Pyritinol increases neutrophil chemotaxis. This means that the white blood cell called a neutrophil travels to the site of an infection and releases free radicals to kill germs. Most of the pus that forms in wounds is made from neutrophils. In the process it promotes an inflammatory reaction, which can become severe. Pyritinol not only increases the number of neutrophils traveling to the infection, it prevents the inflammation from becoming too severe. Interestingly enough, it also prevents the sugar-induced loss of immune function. Normally, the sugar in a can of soda can inhibit immune function by stopping neutrophils from killing germs. This can be so severe that a loss of 50 to 80% function for up to five hours can take place. Pyritinol prevents this immune dysfunction.

Pyritinol also increases mental vigilance by increasing nerve activity in the locus coeruleus of the brain. This part of the brain is especially prone to damage in Alzheimer’s Disease. Pyritinol literally increases brain power as measured by an electroencephalogram (EEG) which also results in better memory according to studies.

Very few side effects have been noted with Pyritinol.

A wide range of doses has been used in Pyritinol studies. These have ranged from as low as 100 mg twice daily to 200 mg three time’s daily or 200 mg four times daily. For anti-aging, cognition enhancing or antioxidant purposes, 100 mg Pyritinol two or three times daily is generally safe and adequate. Higher doses (400 - 1000 mg daily) should probably be used only occasionally. Pyritinol may be taken either on empty stomach or after food, as desired. Persons only prone to insomnia should probably only take Pyritinol morning and early afternoon. There may be a mutual enhancement of action between Pyritinol and other nootropic substances, allowing/requiring lower doses of some or all the drugs in order to avoid an over-excitation effect.

[Above info from]

Pyritinol: The European Smart Drug

The drug Pyritinol is used in Europe for the treatment of several forms of neurologic impairment. Based upon published research, this therapy shows benefits in the treatment of early stage Alzheimer’s disease, stroke, vertigo, head trauma, and age-associated mental impairment.

The evidence shows that pyritinol enhances neuronal metabolic function. It works by increasing brain-cell energy levels so that youthful, cognitive function can be at least partially restored. There is a large volume of human clinical data supporting the safety and efficacy of this European therapy.
The pyritinol molecule is structurally similar to vitamin B6, but functions in the brain in a different way. The dose of pyritinol used in most of the human clinical studies is one 200-mg capsule taken 3 times a day.

(In referring to the studies described below, a “double-blind” trial is one in which neither the subjects nor the persons administering the treatment know which treatment a subject is receiving. When a trial is “randomized,” it means that subjects are assigned to treatment groups in a known probability distribution, to produce more accurate results.)

The journal Alzheimer’s Research (2/3 1996) reported on a double-blind study conducted in the United States in which pyritinol was compared to Hydergine and placebo (a dummy treatment) in treating 100 patients with Alzheimer’s disease. Two measures of cognitive function were used to assess treatment effects.

After 12 weeks of treatment, “the results indicated that treatment with pyritinol was associated with a significant and continuous improvement in cognitive functioning over the course of the study, while treatment with Hydergine was associated with a more modest improvement that tended to plateau early in the treatment phase.”

In the journal Neuropsychobiology (26(1-2) 1992), a 12-week, double-blind clinical trial was performed to investigate the benefit of pyritinol in the treatment of several forms of senile dementia. A total of 156 patients were allocated to either of two groups: the “senile dementia of the Alzheimer’s type” group, or the “multi- infarct dementia (stroke)” group.
In a 12-week, double-blind treatment, the researchers used three well-established tests to evaluate cognitive function. In addition, EEG brain mapping was employed to measure brain-cell function.

The doctors stated, “The therapeutic efficacy of pyritinol was clearly demonstrated by confirmatory analysis as the drug was statistically significantly superior to placebo in all three target variables. The EEG mapping demonstrated significant differences between placebo and pyritinol.
Based on the results of this trial, it can be accepted that the therapeutic effect of pyritinol is superior to placebo in patients with mild to moderate dementia of both degenerative (Alzheimer’s) and vascular (stroke) etiology.”
As reported in a study in the British journal International Clinical Psychopharmacology (January, 1989), 26 patients with Alzheimer’s disease were randomly assigned in a double- blind trial of pyritinol versus placebo. The patients had a mild to moderate degree of dementia.

The results of the study showed that “pyritinol was associated with a significant improvement in cognitive performance. Regional cerebral blood-flow data showed that treatment with pyritinol normalized the pattern of blood flow increase during activation and improved the score on the test used for activation.”

In the German journal Pharmacopsychiatry (September 1986), the effects of pyritinol were investigated in a placebo-controlled, randomized, double-blind study in geriatric patients suffering from cerebral functional disorders, with a moderate to severe degree of chronic brain syndrome. In a previous study, a rise in the vigilance (wakefulness, alertness) level was demonstrated in patients undergoing pyritinol treatment. Data from 107 patients were included in the statistical analysis, 54 on pyritinol and 53 on placebo. No notable adverse drug reactions were observed.

The doctors reported, “Statistically significant results were found in favor of pyritinol, compared with placebo, in both the level of clinical symptomatology & the performance level. Particularly impressive was the superiority of pyritinol in the factor ‘social behavior.’”

In the journal Neuropsychobiology (24(3) 1990), 12 healthy male volunteers received pyritinol in doses of 600 or 1,200 mg per day, or placebo for three days according to a randomized, double-blind design. On the first and third days of each of the three treatment periods, subjects completed a battery of psychological tests. The doctors reported, “Significant improvements in the Critical Flicker Fusion test and the Choice Reaction Time test were found after pyritinol.”

In a study conducted at the Max-Planck-Institute of Neurology and published in Annals of the New York Academy of Sciences (640, 1991), pyritinol was tested along with piracetam and phosphatidylserine in Alzheimer’s patients. Positron emission tomography (PET) was used to measure the brain’s energy metabolism (brain functioning).

The doctors noted that glucose metabolism decreases slightly with age, but Alzheimer’s disease shows severe deficits in glucose metabolism. In the assessment of the effects of pyritinol on disturbed glucose metabolism, the doctors stated, “PET studies showed general increases in glucose utilization with piracetam, pyritinol and phosphatidylserine.

In the Journal of International Medical Research (9/3, 1981) 270 patients suffering from different forms of brain injury were treated with pyritinol for 6 weeks. It was shown that, “compared with placebo therapy, pyritinol produces statistically significant improvement in clinical and psycho neurological manifestations. It is concluded that pyritinol is a drug of therapeutic benefit in the treatment of the [results] of cerebral trauma.”
In Pharmatherapeutica (England, 2/5, 1980) a double-blind, placebo- controlled trial was carried out on 40 patients suffering from moderately advanced dementia. The patients were allocated randomly either to pyritinol or placebo for three months. Assessments of cognitive function were made pre-treatment and monthly up to three months, and then at follow-up at six months. The doctors concluded, “Patients on pyritinol showed significantly higher levels of improvement than did those on placebo. Laboratory tests conducted throughout remained within normal limits for both groups.”
In the German journal Med. Klin. (73/31 1978), 161 patients with chronic organic brain syndrome (average age 64 years) were treated with various doses of pyritinol for different periods of time. The doctors stated, “Statistical analysis of the data showed the success rate of treatment increases significantly with increasing dose & duration of [Pyritinol].

In the French journal Ouest Medicine (29/1 1976), pyritinol was tested on people who suffered from vertigo. The doctors described a complicated mechanism by which pyritinol was effective against vertigo, and reported the following:

“In a clinical experience with 60 cases of vertigo, the author obtained a cure rate of 83.33 percent, accompanied by an improvement in the patients’ mental and social state. The drug was tolerated well by patients of all ages.”
The Czech journal Cs. Pediat. (29/10 1974) reported that pyritinol was tested on 41 children (28 boys and 13 girls) with various diseases of the central nervous system. The doctors reported, “In severe contusions of the skull with apallic syndrome (a total of 9 children), improvement was recorded in the majority, & marked improvement in 33%.

In meningo-encephalitis (8 children), treatment was successful in 50% the patients; in infantile cerebral palsy and malformations on the brain (19 children), treatment was successful in about 33% of cases. In minor disorders of the brain (5 children), the effect was smallest. According to these results, pyritinol treatment offers a certain contribution to treatment used in pediatric neurological practice.”

Those with any of the neurological impairments that pyritinol has been documented to alleviate should consider taking 200 mg 3 times a day under the care of a physician, preferably a neurologist. It appears that pyritinol can produce both an immediate and a cumulative beneficial effect on neurologic function.

Those seeking to preserve and enhance cognitive function may consider trying two 200-mg capsules of pyritinol early in the day in place of drugs such as Hydergine. It is suggested that pyritinol be taken early in the day because its cerebral-energizing benefits can interfere with sleep if taken too close to bedtime.

[Info adapted from]

Pyritinol In Dementia

Neuropsychobiology 1992;26(1-2):65-70
Therapeutic efficacy of pyritinol in patients with senile dementia of the Alzheimer type (SDAT) and multi-infarct dementia (MID).
Fischhof PK, Saletu B, Ruther E, Litschauer G, Moslinger-Gehmayr R, Herrmann WM. Psychiatric Hospital Baumgartner Hohe, Vienna, Austria.

This trial was performed to investigate the efficacy of pyritinol in the treatment of senile dementia. Initially, a total of 183 inpatients were screened for eligibility. Of 164 patients who met the inclusion criteria, 156 completed the trial. Allocation of the patients to the Senile Dementia of the Alzheimer Type group or the Multi-Infarct Dementia group was based on the Hachinski Ischemic Score, computed tomography scans and electroencephalographic (EEG) findings. In a 12-week double-blind treatment phase either 200 mg pyritinol dihydrochloride-monohydrate or placebo was given 3 times daily. Confirmatory statistics included item 2 of the Clinical Global Impression, the total score of the Short Cognitive Performance Test (Syndrom Kurz Test) and the factor ‘cognitive disturbances’ of the Sandoz Clinical Assessment Geriatric scale. In addition, data on tolerance, of EEG brain mapping and of a responder analysis were evaluated based on descriptive statistics. The therapeutic efficacy of pyritinol was clearly demonstrated by confirmatory analysis, as the drug was statistically significantly superior to placebo in all 3-target variables. The clinical relevance of the outcome was underlined by the analysis of the descriptive variables and by the convergence found at the different observation levels. The EEG mapping demonstrated significant differences between placebo and pyritinol, with the latter decreasing slow and increasing fast alpha and beta activity, which reflects improvement of vigilance. Based on the results of this trial, it can be accepted that the therapeutic effect of pyritinol is superior to placebo in patients with mild to moderate dementia of both degenerative and vascular etiology.

Clin Psychopharmacol 1989 Jan;4(1):25-38
Pyritinol treatment of SDAT patients: evaluation by psychiatric and neurological examination, psychometric testing and rCBF measurements.
Knezevic S, Mubrin Z, Risberg J, Vucinic G, Spilich G, Gubarev N, Wannenmacher W. Department of Neurology, University Hospital Centre, Zagreb, Yugoslavia.

A group of 26 patients with the diagnosis of Senile Dementia of Alzheimer type (SDAT) was included by random assignment in a double-blind, cross-over trial of pyritinol versus placebo. The patients had a mild to moderate degree of dementia. Psychiatric and neurological examination, psychometric testing, and measurement of the regional cerebral blood flow (rCBF) at rest and during mental activation were used to assess treatment effects. The results of the study showed that pyritinol was associated with a significant improvement in cognitive performance. RCBF data showed that treatment with pyritinol normalized the pattern of blood flow increase during activation and improved the score on the test used for activation.

Pharmatherapeutica 1980;2(5):317-22
A placebo-controlled study of pyritinol (‘Encephabol’) in dementia.
Cooper AJ, Magnus RV.

A double blind, placebo-controlled trial was carried out on 40 patients suffering from moderately advanced dementia. The patients were allocated randomly either pyritinol (800 mg daily) or identical placebo for 3 months. Assessments using a modified Crichton Geriatric Behavioral Rating Scale were made pre-treatment and monthly up to 3 months, and then at follow-up at 6 months. Patients on pyritinol showed significantly higher levels of improvement than did those on placebo. Laboratory tests conducted throughout remained within normal limits for both groups.

Alzheimer’s Research, 1996; 2(3):79-84
Efficacy of Pyritinol versus Hydergine upon cognitive performance in patients with Senile Dementia of the Alzheimer’s type: A double-blind multi-center trial.
George J. Spilich, Wolfgang Wannenmacher, Antonio Duarte, Marco Buendia, J. Toro Gómez, Sergio Ramirez, Amalia Anaya, and Enrique Otero.

In this multi-center trial, 100 patients with the diagnosis of Senile Dementia of the Alzheimer’s type (SDAT) of mild to moderate severity were randomly divided into two treatment groups and, following a placebo wash-out phase, were administered either pyritinol or hydergine for 12 weeks in a double-blind, randomized parallel comparison. Two measures of cognitive functioning were employed to assess treatment effects. The results indicated that treatment with pyritinol was associated with a significant and continuous improvement in cognitive functioning over the course of the study while treatment with hydergine was associated with a more modest improvement that tended to plateau early in the treatment phase. We interpret our results to indicate that treatment of mild to moderate Alzheimer’s disease with pyritinol is more likely to result in an improvement in cognitive performance than is a similar course of treatment with hydergine. Our results also suggest that continued treatment with pyritinol is often accompanied by continued improvement in cognitive function, while treatment effects with hydergine are mostly limited to those observed in the initial 6 weeks of intervention.

Pyritinol In Children

Pediatr Res 1975 Sep;9(9):717-21
Pyritinol hydrochloride and cognitive functions: influence on children in slow learner classes.

Walti U, Kuenzler M, Schild J, Vassella F, Pavlincova E, Bircher J, Herschkowitz N.

Pyritinol-HCl was tested for its impact on the cognitive functions of children with learning disabilities. This study is a contribution to scientific discussion on the complicated methodologic problems in evaluating the clinical efficacy of psychopharmacologic agents. Sixty-seven pupils of slow learner classes between the ages of 11 and 16 years were treated for 6 months with 300 mg pyritinol-HCl/24 hr or placebo under strict double-blind conditions. Drug intake was stimulated and controlled by means of intense psychosocial interaction with the mothers of the subjects. The dependence variables used to test medication effects were 22 parameters of cognitive performance measured in psychologic tests for perceptual and intellectual functions that were administered immediately before and after the medication phase. First the gainscores before and after treatment with pyritinol or placebo within the 22 cognitive parameters were statistically compared. In addition, an analysis of covariance on the corrected results of the second test (treating the results of first testing as covariates) and a two group discriminant analysis for overall differences were performed. None of the 22 parameters showed statistically significant treatment effects with respect to average performance (t (pyritinol - placebo) = 1.96 to 1.31), neither could the two groups be separated by discriminant analysis (Hotelling’s T2 = 35.4, df - 22 and 43, P = 0.465). With respect to a variability of gainscores, however, in four parameters there was a significantly higher variance in the pyritinol group (F = 1.85-2.33, P less than 0.05, less than 0.02, respectively). This fact may signify that pyritinol-HCl had different effects on different subjects. By means of prognostic stratification we therefore attempted to define objective criteria for a selection of subjects with probable positive treatment effects. None of the 15 tested criteria, such as body weight, age, perceptual handicaps, or reduced short term memory, IQ range, proved, however, to be critical for a prognosis of pyritinol effects within the present test population.

Zh Nevropatol Psikhiatr Im S S Korsakova 1979;79(10):1431-4
Analysis of the effectiveness of treating children with different forms of intellectual deficiency with piriditol

Lupandin VM, Ermolina LA, Zykov MV, Korobeinikova II, Dzhebrailova TD.

The clinical efficacy of piriditol treatment in children with intellectual insufficiency was studied by means of special techniques, determining the velocity of visual information processing (VVIP) and short-time visual memory (SVM), which reflects the functional state of the brain. Piriditol was administered to 50 children aged from 7 to 12 years. The clinical state was characterized as mental retardation, due to mild organic brain lesions or oligophrenia in the form of mild debility. The use of special techniques (VVIP and SVM) for the study of intellectual activity permitted to analyze more differentially the stimulating and sedative effect of piriditol, to detect the new property of the drug, i.e. to remove the processes of fatigue in the brain tissues. A positive effect of the treatment was most marked in children with mental retardation rather than in oligophrenic patients.

Pharmatherapeutica 1981;3(1):40-5
Tamitinol in paedopsychiatric out-patient therapy.

Sanz R, Bettschart W, Reinhardt B.

A study was carried out in 11 children, ranging in age from 7 to 12 years, to determine the clinical effect of tamitinol, in addition to psychotherapy, in alleviating disturbances of learning and behaviour. Tamitinol was administered as one 100 mg tablet per 10 kg body weight daily for 8 weeks. Assessments were made of the patients’ mental condition using a 7-point rating scale, before and during treatment. Global response to treatment and tolerance were evaluated at the end of the trial by the clinician and the patients (or parents). Significant improvement was noted in 7 of the 10 children who completed the study. Six of the 13 psychiatric symptoms evaluated by the clinician were significantly improved (p less than 0.01). The drug was well tolerated by all patients.

Cs.pediat. (Czechoslovakia), 1974, 29/10 (562-564)
Neurologic Diseases in Children

41 patients (28 boys & 13 girls) with various diseases of the central nervous system were treated by oral administration of pyritinol in addition to the usual therapy. Before, during and after termination of treatment, neurological, psychological and EEG examinations were made to evaluate the effect of pyritinol. The patients were divided into 4 main groups. In severe contusions of the skull with apallic syndrome (9), improvement was recorded in the majority, & marked improvement in one-third. In meningoencephalitis (8), treatment was successful in half the patients; in infantile cerebral palsy and malformations on the brain (19), treatment was successful in about one-third of cases. In minor disorders of the brain (5), the effect was smallest. According to these results, pyritinol treatment offers a certain contribution to treatment used in pediatric neurological practice.

J Hyg Epidemiol Microbiol Immunol 1983;27(4):373-80
Brain maldevelopment and delayed neuro-behavioural deviations, induced by perinatal insults, and possibilities of their prevention.

Benesova O.

Noxious insults interfering perinatally lead to disorganization of normal perinatal brain development characterized by growth acceleration and intensive histogenesis and known as a sensitive “vulnerable” period of CNS development. Thus induced abnormities, sometimes very discrete, give rise to functional pathology that becomes apparent gradually during maturation as neurobehavioural deviations. For the study of these pathogenetic processes, two experimental models were established. Rat was chosen as an advantageous model animal since the “brain growth spurt” occurring in man in the third trimester of gravidity is shifted postnatally in this altricial species. Prolonged neonatal malnutrition (days 1-40) lead in adult rats to behavioural abnormities (hyperactivity, stereotypy, decreased adaptability, aggressivity) associated with biochemical and electrophysiological alterations in the brain. But this multifactorial and long-term insult was not suitable for more precise analysis. Therefore short-term inhibition of protein synthesis was induced in 7-day-old rats by cycloheximide that resulted in delayed behavioural deviations (hyperactivity, decreased habituation, learning deficit, motor incoordination) connected with permanent morphological, biochemical and endocrinological alterations. These models were used for testing brain maldevelopment-regulatory action of nootropics. Pyritinol administered for 7-10 days following the noxious intervention prevented the brain maldevelopment and functional disturbances in both experimental models. Favourable effects of early and long-term pyritinol treatment on neuro-psycho-pathological sequels of perinatal distress were confirmed in clinical controlled prospective study of 128 high-risk newborns.

Pyritinol Studies

Neurol Neurochir Pol 1981 Jul-Aug;15(4):447-51
Comparative evaluation of psychoactive drugs used in patients with subacute and chronic cerebrovascular disorders

Wasilewski R, Lebiediewa N, Kozlowa E, Wolkow W.

The report is based on 315 patients with subacute and chronic cerebral circulatory disturbances caused mostly by atherosclerosis aged 30 to 82 years, treated for 1-6 months. In 90 cases Piracetam (Nootropil) was given, 107 received Piritinol (Encephabol, Enerbol), 77 Piriditol, 41 Centrophenoxin. The patients were allocated randomly to these groups. In the treated patients improvement was achieved in a considerable proportion of cases (44-82%) treated with different drugs. This improvement manifested itself as regression or decreased intensity of neurotic complaints, labyrinthine-cerebellar signs, pyramidal signs, anxiety and fears, improvement of recent memory, attention, psychomotor activity. The best results were obtained with Nootropil, moderately good with Centrophenoxin, Encephabol, and poor with Piriditol. Drug tolerance was best with Encephabol, while that of other drugs was slightly worse. The only disquieting symptoms was activation of epileptic seizures in several patients treated with Nootropil or Centrophenoxin. The best way of administration was giving the drugs in two doses in the morning hours and at noon. The authors regard as useful the treatment of patients with subacute and chronic cerebral circulatory failure with psychoenergizing drugs.

Farmakol Toksikol 1980 Jul-Aug;43(4):417-21
Effect of pyriditol on drug metabolism

Avakumov VM, Kovler MA.

Pyriditol (encephabol, enerobol, pyrithioxin, etc.), a disulfide derivative of pyridoxin, exerts an inhibitory effect on hexobarbital and amphetamine metabolism i vivo and on ethylmorphine N-demethylation in vitro. In the latter case the inhibition proceeds according to the mixed type of action. Pyriditol potentiates the hypnotic action of hexobarbital and barbital as well as the effects of amphetamine stereotypy. The mechanism of the potentiating of hexobarbital and amphetamine effects is of combined character and is conditioned both by the physiological properties of pyriditol and its inhibitory effect on hexobarbital and amphetamine metabolism.

Neuropsychobiology 1990-91;24(3):159-64
Psychopharmacological effects of pyritinol in normal volunteers.

Hindmarch I, Coleston DM, Kerr JS. HPRU, Robens Institute, University of Surrey, Guildford, UK.

Twelve healthy male volunteers received pyritinol 600 or 1,200 mg or placebo for 3 days according to a randomised, double-blind crossover design. On the 1st and 3rd days of each of the three treatment periods subjects completed a battery of psychological tests including Critical Flicker Fusion (CFFT), Choice Reaction Time (CRT), tests of memory and subjective drug effects at 1, 2, 4 and 6 h after dosing. Significant improvements in CFFT and CRT were found after pyritinol. There were no significant differences on the other tests; however, the observed enhancement in performance could be attributed to the effect of the drug.

J Int Med Res 1981;9(3):215-21
Therapeutic effect of pyritinol on sequelae of head injuries.

Kitamura K.

Two hundred and seventy patients suffering from the sequelae of different forms of brain injury have been treated orally with pyritinol 200 mg three times a day for a period of 6 weeks. It has been shown that, compared with placebo therapy, pyritinol produces statistically significant improvement in the clinical and psychoneurological manifestations. It is concluded that pyritinol is a drug of therapeutic benefit in the treatment of the sequelae of cerebral trauma.

Anaesthesist 1979 Nov;28(11):530-2
Use of encephabol in anaesthesia and post-anaesthesia resuscitation.

Papatheodossiou N.

On the basis of good results in a pilot study of 40 patients who had undergone anaesthesia for various surgical operations, infusions of pyritinol was tested under controlled double-blind conditions on 60 further patients. Pyritinol 600 mg was infused immediately after anaesthesia. The aim of this study was to verify the favourable effect on the post-anaesthesia phase. It was shown that pyritinol significantly shortens the wakening time and, furthermore, positively influences the subjective feeling of the patients after anaesthesia.

MMW Munch Med Wochenschr 1978 Sep 29;120(39):1263-8
The effect of pyritinol on the human cerebrovascular circulation (author’s transl)

Herrschaft H.

The change in global and regional cerebral circulation after intravenous administration of pyritinol was investigated in 14 patients with acute or subchronic cerebral ischemia. The measurement of the cerebral circulation was performed by intraarterial isotope clearance with 133xenon using a multidetector apparatus. With a single administration of pyritinol (400 mg) there was a statistically significant increase in the cerebral circulation in the gray matter by 6.7 ml/100 g/min corresponding to 9.7% (p less than 0.01) 10 minutes after the end of the drug injection. In the areas of all portions of the brain with defective circulation there was a significant increase in blood flow by 8.9, 0.8 and 3.2 ml/100 g/min (gray matter, white matter, total substance), corresponding to 12.3%, 4.4% and 8.1%. In areas with a normal initial status, the increase in blood flow attained statistical significance in the gray matter only (p less than 0.05).

Electroencephalogr Clin Neurophysiol 1978 Jan;44(1):1-7
N1—P2 component of the auditory evoked potential during alcohol intoxication and interaction of pyrithioxine in healthy adults.

Krogh HJ, Khan MA, Fosvig L, Jensen K, Kellerup P.

The auditory evoked potential was used to assess the effect of alcohol intoxication (1 g/kg) and pyrithioxine (7 mg/kg) on 9 adult subjects. Its components in the latency range 50—250 msec (N1—P2) were studied for 6 g 30 min, during a constant level of alertness. Four periods were considered: alcohol alone, alcohol plus pyrithioxine, pyrithioxine plus alcohol and placebo. With alcohol alone the N1—P2 amplitude was small in the first part of the test and large in the second part as compared to placebo values. Pyrithioxine antagonism was greatest after alcohol had been resorbed. The placebo period indicated that amplitude changes were not due to long-term habituation, when the subject was kept alert.

Med Klin 1975 Jun 27;70(26):1133-8
Neurophysiologic control during treatment of cerebral ischaemia with danaden retard (author’s transl)

Klensch H, Hoffmann HR.

After a three month treatment with Danaden retard (Encephabol + nicotinic acid) a group of patients suffering from cerebral ischaemia showed (in contrast to an untreated group) a significant reduction of slow waves in the EEG, a significant improvement of the audiogram, a reduction of the optic and acoustic reaction time and of the peak latency of the visual evoked potentials.

Eur Neurol 1975;13(4):285-303
Facilitation through hyperventilation of therapeutic effect of pyrithioxin in cerebral infarct patients.

Stoica E, Enulescu O, Gheorghiu M.

A method of treatment consisting in administration of a neurodynamic drug, pyrithioxin, combined with a short period of hyperventilation (HV) was applied in cerebral infarct patients with hemiplegia. The combination was superior to pyrithioxin alone for the motor recovery of these patients. In some cases, it induced immediately a partial restoration of motility. The combination constantly brought about an increase in urinary excretion of norepinephrine and vanilmandelic acid, which failed to occur after pyrithioxin or HV alone. HV appears to facilitate the neural effects of the drug by promoting its transfer into the CNS.

“You see, I don’t want to do good things, I want to do great things.” ~Alexander Joseph Luthor

I know Lewd Ferrigno personally.


Idebenone is an analogue of Coenzyme Q10.
In most respects, Idebenone shares its traits with Coenzyme Q10. Like Coenzyme Q10 is might be useful for aging. It differs from it in some important ways, which may make it more useful.
Under certain circumstances, Coenzyme Q10 (CoQ10) may become a pro-oxidant. These circumstances are conditions in which hypoxia or lack of oxygen occurs. In cases of shock, heart attack, stroke, or poor circulation, CoQ10 auto-oxidizes and unleashes massive amounts of various free radicals that damage delicate tissues and because CoQ10 is necessary for electron transport and ATP (chemical energy) production, cellular death may ensue. Idebenone, on the other hand, suppresses free radicals and continues ATP production in hypoxic situations. This may make it a useful supplement for individuals at risk for those conditions.
Other important traits of Idebenone not shared by CoQ10 include the ability to raise the brain’s serotonin levels like the SSRI antidepressants (Prozac) and it also increases the brain levels of nerve growth factor. Another trait is to protect the myelin sheath from damage as well as the mitochondria that has important implications in Multiple Sclerosis.
The ability to enhance serotonin production occurs even under less than optimal conditions such as those whose diet contains little L-Tryptophan.
Naturally, nerve growth is a desired result in many conditions. In Alzheimer’s Disease, for example, several studies show dose dependent improvements when compared to placebo as measured by different tests when taking Idebenone. An abstract said, “Treatment with idebenone was found effective on memory, attention, and orientation and in slowing down the natural progressive worsening of the disease.”
The following conditions may benefit from Idebenone: Brain enhancement as a nootropic, stroke, Alzheimer’s, dementia, surgical candidates, cardiovascular, MS, other demyelination conditions, aging, depression, Friedreich’s Ataxia, and liver problems.
Few adverse reactions have been noted with this substance even at doses of 900 mg daily.
Take 45-135 mg daily. It is best taken with a meal.

[Above Info from]

Idebenone: The Ultimate Anti-Aging Drug
By James South MA
Idebenone (IDB) is a synthetic analog (variant) of one of life’s most essential biochemicals, coenzyme Q10 (CoQ10). CoQ10 is an important antioxidant component of the lipid (fatty) membranes that surround all cells, as well as the lipid membranes surrounding the various organelles (“little organs”), such as mitochondria and microsomes, inside cells.
CoQ10 is also an important member of the “Electron Transport Chain” (ETC) within mitochondria, which are the “power plants” of the cell. Most of the oxygen we breathe is used inside the ETC to produce much of the ATP bioenergy that powers virtually every activity of our cells and bodies. Without CoQ10, or a good substitute, human life quickly ends, and IDB is a “better CoQ10” that has been extensively researched the past 15 years.
CoQ10’s pro-oxidant action
When blood flow is seriously reduced to any part of the body, as in a heart attack, stroke, trauma, shock, or chronic poor blood circulation- cellular/ mitochondrial oxygen (O2) levels quickly drop in the affected region. Yet because O2 is seven to eight times more soluble in the lipid zones of cell membrane, compared to the watery compartments of the cell, there is still sufficient O2 remaining in the membranes of cells and organelles, as well as in the ETC, to auto-oxidize CoQ10. As the CoQ10 auto-oxidizes, hydrogen peroxide, superoxide and hydroxl free radicals are rapidly formed in massive numbers. These free radicals quickly damage cell/ organelle structure and function, as well as rapidly halt ATP energy generation by the ETC.
Brain and spinal cord cells are especially prone to such damage, and may be irreparably damaged or even destroyed within minutes.
Why Idebenone is superior to CoQ10
Enter IDB to the rescue! Studies have shown that under the same cellular low oxygen conditions that cause CoQ10 to act as a pro-oxidant producer of damaging free radicals, IDB prevents the free radical dam-age and maintains relatively normal cell ATP levels. In short, while IDB can effectively substitute for CoQ10’s positive and life essential functions, it doesn’t have CoQ10’s free radical producing and energy crashing “dark side” which occurs under hypoxic (low O2) conditions.
IDB’s potential benefits fall into five categories: Antiaging, Energy enhancement, Cognition enhancement, Organ protector and Protector against excitatory amino acid neurotoxicity.

Idebenone - The anti-aging benefits
The mitochondrial power plants produce over 90% of all cellular ATP bioenergy. They are also generally the richest sites in CoQ10 (or IDB). Mitochondrial DNA (mtDNA) allows mitochondria to reproduce them-selves.
While the DNA in a cell nucleus comes from both our parents, mtDNA comes exclusively from our mother’s mtDNA. There are typically two or three copies of mtDNA in each mitochondrion, with average 1000 mitochondria per cell. Because mtDNA exists in the “heart of the fiery furnace” where electron “sparks” are constantly leaking as ATP is produced in the ETC, mtDNA is far more prone to free radical electron damage than is the DNA in our cell nuclei that contains the “blueprint” for our entire organism.
At the same time, the repair capacity of mtDNA is much less than that of our cell nucleus DNA. As a consequence, over the course of a lifetime our mtDNA becomes ever more damaged, and the mitochondria produced there from become ever more ineffective at energy generation. Studies comparing heart tissue from young people with that from elderly people have shown almost no significant mitochondrial dysfunction in young hearts, with significant, often severe mitochondrial dysfunction in elderly hearts.
The cells that are most susceptible to mitochondrial energy depletion with advancing age are the brain, skeletal muscle and heart muscle cells. IDB thus offers a prime anti-aging effect here in several ways. Unlike CoQ10, even under the low O2 conditions that may occur periodically over a lifetime, IDB will serve as a powerful mitochondrial free radical quencher, lessening the ever-increasing mtDNA damage that occurs with age.
IDB will work even better than CoQ10 within the ETC to keep energy production high, even under hypoxic conditions. This is especially critical to brain and heart cells that may be rapidly damaged during low ATP production episodes that occur due to poor tissue oxygenation.
Idebenone - Energy enhancement
Iron is a “dual edged sword.” It is absolutely essential for life, it plays a central role in ATP generation in the ETC. Yet iron can also be a powerful initiator of free radical production and cell structural damage, especially under low O2 conditions.
This occurs, for example, during stroke, and during the gradual onset of Parkinson’s disease. Studies have shown that IDB can tightly couple oxidation to energy production. This prevents iron ions from wastefully and toxically, diverting O2 to producing free radicals inside the mitochondria, instead of energy.
Studies have shown that IDB can almost completely eliminate this, diverting 10% of cellular O2 away from toxic iron induced free radical generation, to beneficial ATP energy production under hypoxic conditions. Mild cellular hypoxia can occur even from intense exercise, or even from mild exercise done by out of shape “couch potatoes.”
Idebenone - Cognition enhancement
A variety of studies using brain cells, (animal and humans) have shown IDB’s ability to enhance brain structure and function. Human and animal studies have demonstrated that IDB can enhance serotonin production, even under far less than optimal conditions, as e.g. with a very low tryptophan diet, or in patients with cerebrovascular dementia.
IDB has enhanced cholinergic nerve function and consequent learning ability even under hypoxic conditions, or when an anti-cholinergic drug (Scopolamine) was administered. IDB has increased cellular catecholamine (dopamine, adrenalin and noradrenanlin) production by enhancing cellular uptake of the precursor amino-acid tyrosine. IDB enhances long-term potentiation in hippocampal nerve cells, a key part of memory formation and consolidation. IDB has restored glucose (brain fuel) utilization and ATP production in ischemic (poor blood flow) rat-brain.
IDB has been shown to enhance general cerebral metabolism, lessen the damage from strokes, and has been used to treat Alzheimer’s and other dementias. And like the original nootropic drug Piracetam, IDB has been shown to promote information transfer across the corpus callosum, the membrane separating the right and left-brain hemispheres. This is turn may promote the union/ integration of the logical (yang) and intuitive (yin) halves of the brain/ mind.
Idebenone - Organ protector
As our organs age or are damaged, we age and are damaged. Over a lifetime, blood flow to our organs diminishes due to arteriosclerosis and less efficient heart pumping. This reduces O2 dependent energy production needed for repair, reproduction and normal function of the organ cells. Free radical damage accumulates over time, leaving ever more dead, dying or dysfunctional cells within organs.
At some point a critical threshold is reached when too many cells within an organ are dysfunctional, and they can no longer sustain the organ’s life and function. Then the organ- heart, brain, liver etc. fails. IDB protects organs in many ways; it cushions them against hypoxic (low O2) and/ or ischemic (poor blood flow) damage. IDB enhances both normal and hypoxic ATP energy generation. Each cell in our organs must produce the energy it needs for life and health; cells cannot “borrow” energy from each other.

Idebenone - The free radical quencher
IDB is a powerful antioxidant, more so than CoQ10, and in some studies is 30 to 100 times more effective, than Vitamin E or Vinpocetine as a free radical quencher within the brain cells. IDB lessens the free radical induced mtDNA damage that accumulates acceleratingly over a lifetime, slowing organ damage and aging.
A 1995 study in the Journal of Transplantation compared the organ preserving effects of CoQ10 and IDB. The study measured various factors, such as free radical membrane lipid damage, cell protein damage and cellular energy production under hypoxia conditions. Protection against excitatory amino acid (EAA) neuro toxicity
Glutamic acid and aspartic acid are the two chief EAA neurotransmitters in the human brain. Without them we would be “mental vegetables.” Yet under certain conditions, e.g. stroke or traumatic brain injury- excessive amounts of EAA’s accumulate in the fluid surrounding brain cells, causing damage and even death to nerve and glial cells through free radical mechanisms.
EAA toxicity is at least partly responsible for the neurotoxicity of the recreational drug “Ecstasy or MDMA.” Studies over the past 30 years have also shown that excessive dietary intake of EAA’s may also damage brain structure/ function, especially in children or EAA sensitive adults. The two main dietary sources of EAA’s are the flavor enhancer MSG (monosodium glutamate) and the artificial sweetener aspartame (Nutrasweet®). Also many processed foods (e.g. canned soups, dry roasted spiced peanuts, beef/ chicken bouillon, canned tuna, spices etc.) contain “hydrolized vegetable protein, yeast extract, soy protein isolate” and similar ingredients that are mostly EAA’s.
In studies with various types of nerve cell, as well as oligodendroglial cells (which make up the protective myelin sheaths surrounding many nerves, the so-called “white matter” of the brain). IDB has shown dramatic protective effects against glutamate toxicity.

Idebenone - The summary
With all these powers, IDB should now rightfully take its place in the first rank of anti-aging/ nootropic/ energizer drugs, along with Hydergine, Piracetam, Vinpocetine, and GH3 (and it’s one of my personal favorites!) So who can benefit from Idebenone? The answers are:
1. Healthy people wishing cognitive enhancement and brain energizer effects (it synergizes well with Piracetam, Vinpocetine, Pyritinol and Picamilon).
2. Stroke victims wishing to improve memory, emotional or speech disturbances.
3. Alzheimer’s and cerebrovascular dementia patients.
4. Those preparing for major surgery, especially brain, heart, liver or kidney. Synergizes well with Hydergine.
5. People with heart energetics problems, cardiomyopathy, ischemic heart disease, and congestive heart failure.
6. People with myelination problems, multiple sclerosis or “white matter” stroke injury.
7. Those seeking to increase their general energy and vitality levels.
8. People with especially high endurance energy needs, e.g. cross country skiers, long distance runners, cyclists, and swimmers.
9. Those at risk of EAA brain damage, e.g. people who routinely consume large amounts of aspartame sweetened foods/ drinks, or those who routinely eat MSG or “hydrolyzed vegetable protein” containing restaurant or prepared foods.
10. People wishing to enhance the serotonin boosting benefits of tryptophan or 5-HTP (5-hydroxy-tryptophan) supplements or SSRI drugs, such as Prozac, Paxil, and Zoloft.
11. Those suffering acute or chronic liver damage from poison mushrooms, toxic chemicals, and hepatitis.
12. People desiring a “long haul” broad-spectrum anti-aging drug. Synergizes well with Deprenyl, Hydergine, GH3.
Because of its synergy with other life extension drugs, those also taking any or all of Hydergine, Piracetam, Vinpocetine, Pyritinol, and GH3 may benefit from even just one 45mg tablet a day, especially if taken regularly on a long-term basis. Because idebenone is fat soluble, it is best taken with a fat rich meal, or with lipid absorption enhancing agents such as lecithin or phosphatidyl choline.
Numerous studies have shown that idebenone is well distributed through-out the body after absorption, accumulating in cellular and organelle membranes, as well as in the electron transport chain, exactly where it does the most good!

[Above info from]

“You see, I don’t want to do good things, I want to do great things.” ~Alexander Joseph Luthor

I know Lewd Ferrigno personally.

CDP-Choline (Citicoline)

CDP-Choline (Citicoline) Monograph

Citicoline (Cytidine 5’-diphosphocholine or CDP-choline), a naturally-occurring endogenous nucleoside, is an intermediate compound in the major pathway for the biosynthesis of the structural phospholipids of cell membranes, including neurons. This pathway is termed the Kennedy pathway.

Citicoline is a polarized molecule with a molecular weight of 488.33. It is a white crystalline, very hygroscopic powder, which is soluble in water.

When administered orally, it is absorbed almost completely, and its bioavailability is approximately the same when administered intravenously. Once absorbed, the cytidine and choline disperse widely throughout the body, cross the blood-brain barrier, and reach the central nervous system (CNS), where they are incorporated into the phospholipid fraction of the cellular membrane and microsomes.

The concept that administration of exogenous Citicoline might augment the synthesis of neural membrane phospholipid is attractive, because accelerated replacement or repair plays a critical role in maintaining the healthy function of numerous physiological processes. It has shown therapeutic efficacy in a variety of diseases in which membrane disorder, dysfunction, or degeneration result in cellular and tissue ischaemia and necrosis.

Citicoline activates the biosynthesis of structural phospholipids in the neuronal membrane, increases cerebral metabolism, and increases the levels of various neurotransmitters, including acetylcholine and dopamine. Citicoline has shown neuroprotective effects in situations of hypoxia and ischemia, as well as improved learning and memory performance in animal models of the brain aging. Furthermore, it has been demonstrated that Citicoline restores the activity of mitochondrial ATPase and of membrane Na+ /K+ATPase, inhibits the activation of phospholipase A2 and accelerates the re-absorption of cerebral edema in various experimental models.

Therapeutic Uses
It is suggested that Citicoline may be suitable for the following conditions:
Cerebral Vascular Disease: From ischaemia due to stroke, where Citicoline accelerates the recovery of consciousness and overcoming motor deficit. The clinical testing of Citicoline has challenged the historical concept that one can do nothing for a stroke patient after a certain period of time has transpired after the onset of symptoms. The practicality of a drug that can be administered up to 24 hours after stroke is a key factor in evaluating the potential of Citicoline.

The result of a recent phase 3 clinical trial among patients suffering from ischaemic stroke demonstrated a statistically and clinically significant improvement in the neurological function of patients treated with the optimal dose of Citicoline, 500 mg daily. The potential of Citicoline as a stroke therapy is underscored by other key attributes: its oral dosage form, a 24-hour window of therapeutic opportunity following stroke, and an apparent absence of significant side effects. Preliminary evidence suggests that in a small sub-group of patients, Citicoline may reduce the size of the impact caused by stroke.

Head Trauma of varying severity: In a clinical trial, Citicoline accelerated the recovery from post-traumatic coma and the recuperation of walking ability, achieved a better final functional result and reduced hospital stay.

Cognitive disorders of diverse etiology: Senile cognitive impairment which is secondary to degenerative diseases (e.g. Alzheimer’s disease) and to chronic cerebral vascular disease. Citicoline improves scores on cognitive evaluation scales and slowed the progression of Alzheimer’s disease.

Parkinson’s disease: Citicoline has also been shown to be effective as co-therapy for Parkinson’s disease. Beneficial neuroendocrine, neuroimmunomodulatory, and neurophysiological effects have been described. Considerable experimental evidence of effects of Citicoline on CNS dopaminergic systems has accumulated. After treatment with Citicoline, regeneration of cells in rats with substantia nigra lesions has been demonstrated. Citicoline increases striatal dophamine and tyrosine hydroxylase synthesis.

Citicoline is a safe and effective nutraceutical, and toxicological tests have shown no serious side effects even after prolonged treatment.

Citicoline (CDP-Choline) Article

Neurons, the principal cells of our brain, along with glial cells, are the doorways to memory. These amazing elements of cerebral life are responsible for orchestrating all the functions of cognition. Out of these brain cells arise our diverse abilities to contemplate the sum total of the universe or investigate the very nature of how our neurons actually perform their incredible tasks. Yet without a lot of healthy neurons we would not be able to store, access, or recall the detailed and extensive information that our brains process into thoughts, ideas and even into wisdom. Neurons help make us what we are. They can wake us up or put us to sleep. They can bring us to full mental readiness or render us unconscious. They can bring us into the light or keep us in the dark.

When our brains are working properly, it is like the spontaneous order of a great city, a city of light and energy. Imagine viewing a sped-up film of the taillights of automobiles moving rapidly through the streets of a city — in building after building, you see flickering light as the energy is exchanged from the human neurons that fuel creativity and growth. Like the city, our brains burn bright with energy.

Responsibility to Our Brain

There is no inevitability that the biochemical energy that electrically paints the cityscape of our brains will continue to flow. When our brains falter and the lights dim and start to go out, we can bemoan this fact or take matters into our own hands by preparing in advance. After all, it is our responsibility to take care of our own brain, to pamper it, and to feed its cells the choicest of raw materials. No one else will do that for us. Without adequate attention to brain nutrition, our neurons and glial cells will fail to live up to their potential and die premature deaths.

Fortunately, neuroscience is progressively discovering the secrets of how the brain operates and what it requires to function optimally. One of the principal areas of scientific study has been the research on the membrane that surrounds the neuronal cell and the role that this membrane plays in ensuring proper function of the neuron. Above all, the function of this membrane is to protect the cell; but it also entails the coordination of a high level of communication and much, much more.

It has become increasingly clear that phospholipids — the various fatty-acid mineral molecules that comprise a significant portion of the membrane — play key roles in maintaining brain cell efficiency. Phospholipids are the attendants at the entry gates into our neural cells (and indeed into all the cells of our body) helping to transport substrates as fuel needed for healthy and efficient operation. Phospholipids help maintain and regulate cell membrane integrity, strength, permeability, elasticity, and resistance to stress, among other functions. Without sufficient nutrients to properly maintain phospholipids, we would not be able to think very well. Our lights would grow dim.

The Membrane Donor

More than 30 years of brain research has resulted in a convergence of knowledge about citicoline (cytidine-5’-diphosphocholine; a.k.a. CDP-Choline), a naturally occurring precursor to one of the most important phospholipids, phosphatidylcholine. In addition to its role in neuron membrane structural function, phosphatidylcholine is thought to play a major role in lipid turnover (utilization of fatty acids) and communication signaling. It also acts as a neuroprotector. Citicoline donates the components choline and cytidine (both of which are precursors to the synthesis of phosphatidylcholine), required to form, repair, and even restore function to nerve cell membranes. Cytidine is involved in the synthesis of other phospholipids. In addition, choline promotes the synthesis of acetylcholine, a neurotransmitter intimately associated with cognition. As an information-transmitting molecule, acetylcholine is necessary for proper memory function and is especially important for aging brains.

To summarize, orally supplied citicoline has beneficial physiological actions on cellular function that have been extensively studied and characterized by mechanism. Citicoline has been found to support membrane integrity, enhance acetylcholine formation, and to contribute to such critical metabolic functions as nucleic acids (e.g., RNA and DNA) and protein synthesis. In the brain, in addition to promoting phospholipid synthesis, citicoline also inhibits phospholipid degradation.

Turn on Your City’s Lights with Citicoline

As we age, our quality of life diminishes across the board with declining vision, hearing, and memory, for example. It is characteristic of our advancing years to find ourselves struggling to recall details, facts, and names that were once at our mind’s fingertips. It is as if our mind’s city lights are going out. This is where citicoline can be particularly valuable. Indeed, citicoline induces bioelectrical changes in the brain (that have been measured using a spectral electroencephalogram) showing increased alpha activity. Researchers who have studied the effects of citicoline on electrical activity, specifically regarding mapping and mental performance, have observed that it lights up certain maps of the brain. Areas of the brain, found to be affected by citicoline include the cortex, hypothalamus, and the Purkinje’s cells of the cerebellum.

Citicoline was found to significantly improve memory at the EuroEspes Biomedical Research Center in La Coruna, Spain. When citicoline was given to 24 elderly subjects with memory deficits and without dementia, the results were remarkable. Over a course of four weeks, subjects taking citicoline in oral doses of either 500 or 1,000 mg were found to have improved memory when compared to those taking placebo. Word recall, immediate object recall, and delayed object recall were all significantly improved after citicoline supplementation. When the 24 were divided into groups of eight and tested again, citicoline was found to possess impressive memory-enhancing activity at doses of 300-1,000 mg/day.

Additional benefits included reduction in blood pressure and positive changes in lymphocyte cell count, reflecting immune readiness. The researchers concluded that citicoline improves memory performance in elderly subjects, and that it is suitable to help prevent age-related memory deficits. Citicoline’s mechanism of action is thought to entail cerebrovascular (blood circulation of the brain) regulation and neuroimmune (immune function of the nervous system) actions in the brain. Neuroimmune decline has been reported to occur with advancing Alzheimer’s disease.

As we age, alterations in membrane function may occur because our ability to synthesize phosphatidylcholine decreases at the same time that catabolism (the breaking down) of choline and other related phospholipids increases. The result is impairment of our cognitive function. Experimental studies have shown that citicoline helps increase the total amounts of phosphatidylcholine and other related phospholipids in the brain. Moreover, in some instances citicoline may enhance nerve transmission.

In a surveillance study that took place in Spain, citicoline was given to 2,817 subjects of all ages, but predominantly in the age range of 60 to 80 years old. The subjects were suffering from various neurological problems, mainly insufficient blood circulation to the brain and volume shrinkage of the brain. When they were clinically assessed and neuropsychologically tested after citicoline use, the conclusions strongly suggested that as a choline and cytidine donor, citicoline may improve some of the deficits associated with aging, including dizziness, headaches, insomnia, depression, and memory shortage. The safety of the citicoline was excellent with side effects observed in only about 5% of the subjects, and among the most frequent were digestive complaints in 3.6% of the cases.

Retarding and Preventing Age-Related Cognitive Decline

In a randomized, double-blind, placebo-controlled, parallel group study, 95 older volunteers identified to have relatively inefficient memories, were given citicoline at a level of 1,000 mg/day for three months. The same subjects — consisting of 47 female and 48 male volunteers, 50 to 85 years old — were recruited for a second study that used a crossover design. In the crossover study, subjects took both placebo and citicoline, 2,000 mg/day, each for two months. In the initial study, at 30, 60 and 90 days, the subjects were screened for dementia, memory disorders, and other neurological problems. The crossover subjects were tested at 90 days. While citicoline improved delayed recall on logical memory in both the initial and the crossover study, the lower dose (1,000 mg/day) benefited only those with relatively inefficient memories. In the crossover study, the higher dose (2,000 mg/day) was clearly associated with improved immediate and delayed logical memory. This was true even for those who weren’t memory deficient. The conclusions found citicoline to be of benefit not only for those with pronounced memory problems but also for those older individuals with little-to-no perceivable decline. Thus citicoline may prove effective for helping to prevent age-related cognitive decline, which may be the predecessor of dementia.

A three-month study examined the use of citicoline on 150 aging subjects with primary memory deficits. When administered in repeated cycles of four weeks, with an interval of one week between cycles, citicoline was found to improve cognitive and behavioral efficiency while stabilizing cognitive decline. The subjects were reported to have better memory recall and increased attention span. Citicoline demonstrated this as a long-lasting effect on cognition and behavior of these patients, with improved activation levels and attention responsiveness.

More Independence and Autonomy of Life

The efficacy of citicoline (1,000 mg/day) administered for two 21-day treatment cycles, with a one-week wash-out (after stopping the treatment) period between them, was evaluated for 237 subjects experiencing moderate brain aging. Using a geriatric measurement scale, the study demonstrated that the positive effects of citicoline persisted through the wash-out period with an even further decrease in measurable symptoms of cognitive decline. The most statistically significant improvement was in the area of the ability to achieve an independent and an autonomous life. Also positively affected were human relations and social life as measured by increased interest and attentive capacity with other people. The study concluded citicoline could thus be recommended for functional and social recovery of the elderly who socially withdraw due to age-related
cognitive decline.

Citicoline Increases Vigilance

When rats were deprived of oxygen by reducing the quantity available over a period of 103 days, their behavior was observed at each increment of oxygen deficiency. Twenty-four of the animals were given citicoline by adding it to their food. Citicoline showed a protective effect, increasing vigilance under mild hypoxia (oxygen deficiency), while those not receiving the citicoline lost vigilance, which indicated the possible use of citicoline for cerebral syndromes due to deficient oxygen supply.

Citicoline Helps Level of Consciousness

A multicenter, double-blind, placebo-controlled study of citicoline was conducted to evaluate its effect in patients with acute, moderate-to-severe cerebral infarction (brain tissue that dies due to lack of blood supply, as in a stroke). The patients subsequently suffered moderate to mild disturbances of consciousness, and all were admitted to the hospital within 14 days of these cerebral incidents. One hundred-thirty-three subjects received 1,000 mg/day i.v. of citicoline for 14 days while 139 received placebo. The group treated with choline showed significant improvements in level of consciousness compared with the placebo-treated group. And choline was an entirely safe treatment.

Citicoline Enhances Mechanisms of Memory

Researchers have isolated several mechanisms by which citicoline might work to improve cognitive function, at least in dementia-type disease.
Patients with Alzheimer’s disease (AD) were given a 1,000 mg daily dose of citicoline for a period of one month and were found to have slight improvements in mental performance. The scientists noted reduced brain theta activity and increased alpha activity in specific regions of the brain. Theta activity is associated with mental sluggishness while alpha activity is connected to mental acuteness. There were also indications of citicoline’s favorable effects on the immune system. Malfunctioning immune response mechanisms are believed to be responsible for age-related dementia-type mental decline.

In another study, researchers correlated citicoline’s effects on cerebral blood flow to changes in cognitive function in demented subjects after daily administration for one week. The study group consisted of seven patients with dementia of vascular origin and three patients with dementia of non-vascular origin. The average age of the subjects was 65 years. Cognitive function increased significantly after one week but only for the vascular group, indicating that the mechanism of action involved cerebral blood flow enhancement. These influences were not found in the brains of the subjects with a non-vascular origin of dementia.

Much of the work done with citicoline and age-related degenerative disease has been done by scientists working at the Basic/Clinical Neuroscience Research Center in La Coruna, Spain. In assessing the results of one study, the scientists detected a significant improvement in mental performance after one month of treatment with citicoline in patients with early-onset AD. In these patients, they correlated brain electrical activity data with cognitive decline. Citicoline produced positive bioelectrical changes indirectly as a result of its effect on immunogenic (immune function producing) and/or neurotrophic (growthful nervous system) activity which, in turn, resulted from improvement of the vascular microenvironment. What is remarkable about their conclusion is that it represents a kind of grand theory correlation suggesting: Citicoline enhances vascular function in the brain resulting in strengthened immune function which, in turn, improves bioelectrical activity — all of which translated into cognitive benefits.

Staying Out of Harm’s Way

A passive avoidance procedure was used to measure the ability “to remember to avoid” a noxious and therefore potentially harmful stimulus. The test used 13-month-old mice in order to test the effects that citicoline had on these processes. Half of the mice received 500 mg/kg per day of citicoline orally for four months. The two groups were compared with a third group of younger animals (four-month-old mice). The older mice showed marked impairment in avoiding harm’s way; however, the older mice (treated with citicoline) had significant improvement in their performance 24 hours after learning the task. This study did not examine the effects of citicoline on younger mice.

Young rats, however, were shown to benefit from citicoline in an active avoidance test. Using a maze method of memory measurement, old and young rats with existing memory deficits were given both positive feedback (rewards) and negative feedback (punishment) reinforcement. The old rats (22 months), which were administered 10 mg/kg of citicoline, were tested for retention at 24 hours and seven days after training.
They were found to be able to retain more of what they learned and able to increase the number of correct responses to the adverse condition.

When the same test given to older rats was given to younger ones (five-months old) the results were similar. Other studies, as well, have borne out that citicoline’s memory-enhancing effects are particularly pronounced in animals with memory deficits whether they are old or young, especially when they have pre-existing memory deficits.

Citicoline Matchs Piracetam

Water maze experiments were carried out on 104 male white rats measuring the effects of four nootropic (affecting cognitive function) drugs and citicoline. All investigated substances were administered immediately after morning training with an oral 100 mg/kg dose for a period of five days. The length of time in the water maze and the number of mistakes (entering blind canals) were measured. Only one of the four nootropics, piracetam had any measurable effect, as did citicoline. Piracetam and citicoline both improved rat memory while the other three nootropics showed no effect. In this study, citicoline improved spatial memory as well as the best nootropic.

In one other study, the memory effects of citicoline surpassed that of the premier nootropic drug, piracetam Mice given citicoline in single doses of 25, 50, 100 and 500 mg/kg, one hour prior to training, were found to have significantly enhanced memory retention both at 24 hours and seven days after the memory session. At a dose of 500 mg/kg, piracetam improved the retention in memory tests 24 hours after training, but had no significant effect during the tests performed seven days after the training. In amnesia induced by the drug scopolamine, 100 mg/kg of citicoline not only prevented memory loss but increased memory as well. In preventing loss of memory from induced amnesia, the amount of citicoline found to be effective was only 20% that of piracetam (500 mg/kg). Yet even five times the level of piracetam did not increase memory retention at the same time as citicoline was able to do.

Citicoline Enhances Cognition and Coordination in Animals and Humans

Another interesting benefit of citicoline is its apparent ability to help with cognitive and motor deficits. When injected at a dose of 10 or 20 mg/kg/day for 20 days, 24-month-old male rats showed enhanced learning memory capacity. Only one injection was needed to protect against behavioral alterations caused by an amnesia-producing drug. An improvement in motor performance and coordination were also observed in aged rats.

A double-blind random block trial was carried out on 58 patients suffering from chronic cerebrovascular diseases in order to evaluate the effects of citicoline. The researchers found that citicoline treatment brought about an improvement in awareness and coordination faculties. This effect can be attributed to overall drug action on neural energy metabolism.

Head Injury

Not surprisingly, citicoline has found a role in treating postconcussional symptoms after mild-to-moderate closed-head injury. In one study, 14 young men (admitted to the neurosurgery service with such injuries) were randomized and given 1,000 mg citicoline or placebo. Control groups were matched for age, education, and severity of impaired consciousness. Citicoline produced a greater reduction of postconcussional symptoms than placebo and further analysis revealed a significantly greater improvement in recognition memory for designs. Other areas tested found no differences between placebo and citicoline.

In another study, also blind and randomized, 216 patients with severe or moderate head injury were treated with citicoline. Results found improved general outcome including a trend toward better motor (coordination), cognitive and psychic function for those treated with citicoline. Patients also had shorter hospital stays than those not receiving citicoline.

Free of Side Effects

Interestingly, citicoline is absorbed almost completely, and its bioavailability is approximately the same as when administered intravenously. Once absorbed, citicoline breaks down into cytidine and choline, which are dispersed widely throughout the body. They cross the blood-brain barrier and reach the central nervous system (CNS), where they are incorporated into the phospholipid fraction of the membrane and microsomes. No serious side effects have been found in any of the groups of patients treated with citicoline, which demonstrates the safety of the treatment.

Curiously, citicoline acts to enhance levels of various neurotransmitters including noradrenaline and dopamine levels in the CNS. The heightened activities of these brain molecules have a neuroprotective effect in situations of hypoxia and ischemia, as well as improved learning and memory performance in animal models of brain aging.

Citicoline appears to improve functional outcome and reduce neurologic deficit with 500 mg of citicoline appearing to be the optimal dose. In rat studies no essential differences in the effects of citicoline were established upon oral and intraperitoneal administration.

Citicoline Summary

Many studies have shown that citicoline prevents, reduces, or reverses the negative effects of a deficient blood supply in most human, animal and cellular models studied. Citicoline acts in head trauma models to decrease and limit nerve cell membrane damage, restore intracellular regulatory enzyme sensitivity and function, and limit edema. Considerable accumulated evidence supports the use of citicoline to enhance membrane maintenance, membrane repair, and neuronal function in traumatic conditions that injure the brain.

In rats with posttraumatic motor and spatial memory-performance deficits caused by traumatic brain injury, citicoline increased acetylcholine release in the dorsal hippocampus and neocortex. Eighteen days of citicoline administration resulted in significantly less cognitive deficits than injured saline-treated rats. Citicoline also lessened the memory-disrupting effects of scopolamine. Amazingly, a single-injected administration of citicoline increased extracellular levels of acetylcholine in dorsal hippocampus and neocortex in normal, awake, freely moving rats. It was concluded that spatial memory performance deficits are, at least partially, associated with deficits in central cholinergic neurotransmission and that treatments which enhance acetylcholine release (following traumatic brain injury) may lessen cholinergic-dependent neurobehavioral deficits.

Beneficial effects of exogenous citicoline also have been postulated and/or reported in experimental models for dyskinesia, Parkinson’s disease, cardiovascular disease, aging, Alzheimer’s disease, learning and memory, and cholinergic stimulation.

By activating the synthesis of critical components in cell membranes, citicoline boosts levels of neurotransmitters such as acetylcholine, and enhances cerebral energy metabolism. Citicoline can help preserve and protect proper memory structure and function. Thus, citicoline can be of significant value in helping to prevent age-associated cognitive impairment — something we all naturally suffer … or soon will. It even boosts mitochondrial energy production, causing the re-absorption of cerebral edema, which can be caused by trauma or even stroke.

“You see, I don’t want to do good things, I want to do great things.” ~Alexander Joseph Luthor

I know Lewd Ferrigno personally.


You needa get another hobby.

Check it out guys, no need to have a big dick if you ain't gonna use it!!

There’s probably something wrong with his ctrl+v, since he keeps on pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting and pasting.

And pasting.

"You are entitled to your own opinion, but not your own facts."

Yes, I guess your right. I seem to went a little overboard on the research part. I just wanted to have more documentation and not jump to an over generalizations. Nothing good was on cable so I spent a few hours gleaming the net for information. I guess I got bored with school being out.

I am going to take a break from a bit. This is turning into a doctoral thesis and I am not even in grad school.

“You see, I don’t want to do good things, I want to do great things.” ~Alexander Joseph Luthor

I know Lewd Ferrigno personally.

>>A man with any degree of common sense will not hurt himself with his own hands.>>

I hear ya. Can you believe I watched “Saving Silverman” last night?

Check it out guys, no need to have a big dick if you ain't gonna use it!!

Originally posted by ThunderSS
He is writing a new PDR. :)

What is a PDR?

“You see, I don’t want to do good things, I want to do great things.” ~Alexander Joseph Luthor

I know Lewd Ferrigno personally.

Originally posted by ThunderSS

Damn! I wish I had this earlier. Oh well hindsight is 20/20.

Hmmmmm…….. I need a new focus for my spare time. Maybe I should start up that Meth Lab in the spare bathroom? It is not like we really use it. ;)

“You see, I don’t want to do good things, I want to do great things.” ~Alexander Joseph Luthor

I know Lewd Ferrigno personally.


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