[archyjuice]

Im kinda stuck with this topic and kinda confused about it. Can anyone give me more insight and their opinion on this particular topic?

[azmanam]

Absolutely essential.

Google thalidomide and prilosec vs. nexium for two examples of how chirality is important.

[Procyan]

Have you ever put your left shoe on your right foot.   

[archyjuice]

HEhe i have tried... 

i got a question thats also related to the topic above.

The pros and cons of single enantiomers drugs vs racemates.

From what i understand, a pure enantiomer drug is presumed to be more superior to the racemate. And recent studies stil cant prove that if im not mistaken. However more and more drugs are being researched and industrial are trying to find the pure enantiomers towards current racemix drugs. Why is that??

More insights and opinions ^^

Btw, thanks azmanam. your info really helped.  *Ignore me, I am impatient* the thread up. Need more help on this topic. Im struggling badly in stereochemistry so any extra info will *delete me* Thanks guys!

[BlowUpEverything]

Alexander Shulgin's studies with MDMA are good examples of how chirality can affect action.  200mg of the R isomer of MDMA was reported to have very little effect, while 120mg of the S isomer is very active.  Furthermore, the racemate seems to have a faster onset and greater potency than either isomer individually.  Interesting stuff, really.  Check out his book PiHKAL for more.

[nj_bartel]

Biological processes typically involve large, structurally complex enzymes that either react only with a single stereoisomer or react with different stereoisomers differently.  You can picture this as previously stated - your foot is a reactant, your shoe is an enzyme.  When they bind correctly (right shoe on right foot, vice versa), you can walk properly.  If you were to attempt to bind your left foot to your right shoe, some funky walking would result, or maybe none at all.

[limpet chicken]

Actually, in the case of thalidomide, the stereochemistry is fairly irrelevant, one isomer is a potent teratogen, and does what thalidomide is best known for doing, but the other is not, problem is, the nonteratogenic isomer is enzymatically interconverted to the teratogen in vivo.

So your screwed either way if you happen to be in the womb at the time.

Blowupeverything, good example, Shulgin and Shulgin are two of my heroes when it comes to pharmacology, those two, sheesh, they really broke the mold when that pair came to be, few and far between, and they have cast iron balls, metaphorically speaking, to stand tall against the fascist bullying on the part of the DEA thats been thrown their way (despite Alexander Shulgin WORKING for the bastards at the time, disgusting, it just goes to show, the DEA filth are nothing but a nest of vipers, and will betray even their own at the drop of a hat should it suit them)

Not to mention being the first in many cases to do a human bioassay of so many novel compounds.

And the same goes with MDA (the primary amine counterpart to MDMA, 3,4-methylenedioxyamphetamine), the R isomer I think, is the more active stimulant, while the S isomer is more active as a serotonin releaser/reuptake inhibitor and produces the entactogenic effects, unusually, as its usually the R isomer amongst the more complex (I.E I mean psychedelic/entactogenic) amphetamines thats the more potent by far, as is the case with DOB, DOI, DOC and their likes.

As well as having differing selectivity for enzyme active sites, which can be completely specific for a single isomer, the same can apply to the binding sites on a metabotropic/ionotropic receptor on the surface of a synaptic terminal as well, or a transport protein for a neurotransmitter, for instance, D-amphetamine is taken up by dopamine transporters in the synaptic terminals, enters the vesicles that store dopamine, and displaces it, whilst forcing the transporter to essentially work in reverse, pumping dopamine out into the synaptic cleft, getting one euphoric and twacked off one's mammary apparati, whilst the L-isomer has primarily noradrenergic effects, and as a single isomer, L-amphetamine is jittery and unpleasant to most people (personally I find either, or the racemate just as unpleasant, but thats just me)

Also the stereochemisty of the amino acids in a peptide can alter/abolish activity, with almost all naturally occuring peptides using l-amino acids, as these are the only ones coded for in DNA, with a few exceptions, notably dermorphin, a potent kappa agonist opioid peptide from the frog Phyllomedusa Bicolor (the dow-kietl!), and a few bacterial peptides/enzymes, but on the whole, life on earth uses almost exclusively L-amino acids in protein and peptide synthesis.