Southpaw’s Pharmacology Primer Part II: Stereoisomers of drugs/supplements cont’d.
Southpaw’s Pharmacology Primer Part II: Stereoisomers of drugs/supplements cont’d.
(Please see Part I before reading this)
Molecules may contain several of these asymmetrical twist points. As well as the “L” and “D” we discussed in Part I, “Left” and “Right” may also be described as (-) for left and (+) for right, or “s” —(lower case s, or sinister, Latin for left) or “d” (lower case d, for dexter, Latin for right). Thus, L, (-) and s all stand for lefthanded, D, (+) and d all stand for righthanded isomers. Between themselves, they have specific differences, which I will mercifully not inflict upon you here :)
Example: THC is the psychotrope that gives the classic marijuana high. Specifically, it is L(-) delta 1,6, transtetrahydrocannabinol. L (-) means “left-left”, so the L(-) prefix on the front of that word means specifically it is the double lefthanded twist isomer of THC. Right? Right! See how easy organic chemistry is ? :)
When we synthesize organic molecules that contain isomers, they generally yield what is called a racemic product, meaning a random 50:50 mixture of the left and right handed isomers. Racemers are okay if we understand that half the product is probably inactive, but we don’t like “dirty” mixtures. We may tolerate wankers and layabouts in society, but not in our drug bottles, so we want to isolate and discard the useless isomer(s) and keep only the good stuff. If the molecule in question is a double isomer, only 25% of the yield is any good to us (1/2 of 1/2), and a triple isomer, only 1/8 is any good (1/2 of 1/2 of 1/2). Thats why complex isometric molecules can be quite expensive, because the yield of active product is so low. Not much wheat, and a lot of chaff.
How do we determine if an isomer is “left” or “right” to begin with? We do this optically because it rotates polarized light to the left or right of zero, respectively. A pure left handed isomer would rotate light -90 degrees left of zero, and a pure right handed isomer +90 degrees right of zero, so we know how much contamination there is pretty accurately by how much the test sample is pulled off of + or - 90, if at all. A perfectly racemic mixture would therefore have a net polar rotation of dead nuts zero. An almost pure, but not totally pure, L isomer would rotate, say, to about -85.
More relevant examples: Ephedra is discussed a lot here. L-ephedrine, or levoephedrine is very potent as a stimulant and is used/abused frequently for its properties by dieters and truckers. In this case, its D isomer does have some weak activity (not all wrong handed isomers are comletely inactive). D-ephedrine—or pseudoephedrine— as it is called, is a common decongestant in cough and cold medine, sold under the popular brand name of Sudafed. If you can flip D-ephedrine (pseudoephedrine) to L-ephedrine, you convert a mild decongestant into a potent psychostimulant.
Dextromethorphan is a common cough suppressant ingredient in cough syrups. Among other brands, it is in Robitussin-DM, and is the “DM” in other such medications containing D-methorphan. Its opposite isomer, L-methorphan or levomethorphan, is more potent than morphine, powerful enough to perform surgery with, in fact. Similarly, if you can flip the common over the counter D-methorphan found in cough syrups into L-methorphan, you convert a mild cough suppressant into a powerful opiate narcotic. You would be very popular with drug dealers.
Just some tricks of the trade I am sharing with you.
Hope this helps you understand isomers, and what impact they have on the drugs and supplements you take.
--- Southpaw
