Posted by Xevious on July 28, 2002, at 1:23:59
In reply to Re: Question for you - Xevious » BekkaH, posted by Iago Camboa on July 26, 2002, at 5:00:38
Iago (and others),
Yes, I certainly have much to learn! That's one of the reasons why I'm here, and when I'm speculating, I'm careful to point out as much. However, had you read my post more carefully, you would have observed that I at no point suggested that different people manufacture custom enzymes that "prefer" different enantiomers; I did, however, question the assumption that has been posted here many times before that the d enantiomer of amphetamines (or pstims in general) has high CNS selectivity whereas the l enantiomer has high PNS selectivity. For this assumption, I have found zero evidence outside of a few anecdotal reports made by posters on this site.
From my (albeit limited) knowledge of organic chemistry, in the simplest case, the d enantiomer would simply be metabolised more effectively than the l enantiomer, which would not support the CNS/PNS selectivity assumption. In a more complex case, alternate metabolic pathway(s) would create a metabolite that is PNS selective. In this latter case, the degree of d-vs.-l selectivity evidenced by each metabolic pathway could account for d/l CNS/PNS selectivity. In either case, there is a specific biochemical mechanism responsible for the process of x-amphetamine -> CNS stimulation and/or x-amphetamine -> PNS stimulation.
Here are the facts that I *am* aware of:
d-amphetamine is the more active enantiomer; however, l-amphetamine is also a biochemically active enantiomer. There are several pathways available for the metabolism of amphetamine, including hydroxylation and deamination, each resulting in different intermediate compounds. I do not know if d-amphetamine is the eutomer for each of these pathways. The presence of multiple pathways is responsible, in part, for the fact that different people respond differently to a similar dose of any given compound.
As a scientist, I certainly contend with the idea that one can satisfactorily explain *any* process by repeating a mantra of "it's just a fact of life." If, for example, the medical field took this stance, then we would have no medicines as illness would merely be a "fact of life."
My question to you, Iago, since you have asserted your knowledge in the subject of organic chemistry, is this: if d-amphetamine is indeed more CNS-oriented and l-amphetamine more PNS-oriented, why? Which amphetamine metabolite is responsible for exclusively stimulating the central nervous system while leaving the peripheral nervous system untouched? I ask this question honestly, as I did in my original post, and would appreciate an answer intended to decrease my ignorance as opposed to triumphantly pointing it out to the rest of the world.
Educate me.
-Xevious
> > Xevious,
> > Are you sure that the CNS/PNS stimulation issue of the d and l isomers is only subjective and not scientifically proven? I've read about this in so many places, including some psychopharmacology texts, so I'm wondering whether it is just subjective.
>
> Hi Bekka,
>
> Of course it is you (and all the world with you) who is right about the ACTUAL (OBJECTIVE) differences between the properties of Dexedrine (= d-amphetamine, the 'good' enantiomer) and the l-amphetamine, as is the rule with 99.99% of substances that happen to appear in both l- & d- varieties: the rarer in nature is the two being equally active. And there is NO such thing as people (whose body) 'prefer' the -l variety and people who 'prefer' the -d (that would mean different genetic material (not less!!) and would be impossible for any two individuals of our species).
> It is an absurdity, as impossible as one person whose body had one certain aminoacid of the d-variety instead of the actual one (of the l-variety); that person could not even eat terrestrial food as all life on earth is based on the exact same aminoacids (mainly of the l-variety) and our enzymes are encoded genetically and built that way that they are only able to deal with one and only one of the two (theoretical) possible enantiomers: just the one that happens to appear naturally in our planet. It is the nature of things, as sure as all electrons being negative and protons positive.
> There is no need to 'prove' scientifically that d-amph is much more active and is more CNS oriented & l-amph is more PNS oriented: it is a simple fact of life, one compound happens to have the properties such & such and the other some other properties. In my opinion our friend Xevious is an intelligent guy but has yet to learn many things (as we all have) and get a little more 'common sense' before he can post 100% reliably to his own self-enjoyment and the benefit of all PB community.
>
> Kind regards,
> Iago
>
>
poster:Xevious
thread:113464
URL: http://www.dr-bob.org/babble/20020725/msgs/113989.html