Posted by Iago Camboa on July 29, 2002, at 7:11:48
In reply to Re: Question for you - Xevious, posted by Xevious on July 28, 2002, at 1:23:59
Xevious,
Oh heaven. You look to me like that person who began to criticize all modern Biology textbooks on the grounds that they fail to describe and have in no account three most 'important animals', namely the chimaera, the unicorn and the sphinx. What has one to respond? Perhaps something like this: 'those creatures are never mentioned probably because they don't exist or at least were never described by any biologist; if you feel uncomfortable with that fact try to find one instance of each and describe them in an appropriate publication yourself: perhaps then they find acceptance in science; go ahead and good luck! This I mention without any intention of ridiculing you but to make an important point: in science the 'onus probandi', i.e. the burden of proof is on the ONE WHO AFFIRMS some provocative statement. There is no need for anybody to bother to prove that those hypothetic animals cannot exist, the silence is response enough...
In our case, for anybody who wants to know the truth it is enough to get to a search engin and type the single word 'dextroamphetamine' and hit the enter key: they will find a tremendous wealth of information as is appropriate for one of the most important & useful psychotropic substances ever discovered by man. One will find monografies about the tremendously important medicine 'Dexedrine' (or rather 'dexedrine', as the word came to be felt as a common noun, shorthand for the longer name 'dextroamphetamine'), an indispensable medicine in our world. Now type at the search engin's prompt the word 'levoamphetamine' and press 'enter' again. You will find nothing interesting: there is no medicine based on that chemical compound, for the good reason that it is an useless substance to anyone: if you are interested in its CNS effects, dexedrine is a substance a number of times stronger and devoid of its side effects (due to its unwanted action on the PNS).
Anybody who wants to can get ANY treatise on psychopharmacology and take a look on the chapter where pstims are dealt with: they will find that 'l-amphetamine' is a 'non-entity', compared to the all-importance of its twin (d-amphetamine). I said and repeat it here again: it is a fact of life without appeal that only d-amph is relevant and l-amph is useless. (l-amph was born under an unlucky star, if you prefer things put that way...). And if you feel unhappy with the actual situation go ahead and publish in an appropriate place your ideas about the excellence of l-amph and we will all see the results. Good luck and be happy in your endeavor! Maybe you can convince a drug manufacturer and they put a new medicine into the market, perhaps 'Levedrine' or the like...
About your 'biochemical' reasonings, I'm sorry but they mean to me as much as nothing: they seem to me a cloud of dust thrown to the eyes of fools and simpletons (though I'm by no means an expert either on organic chemistry or on biochemistry or on (psycho-)pharmacology), without any sound contents.
And just take this extra ado. It is also COMMON established knowledge (facts of life without appeal) that alcohol is a depressant of the CNS and caffeine a stimulant thereof. Does it make sense beginning to assert the nonsense that there exist no prove to that effect and then claim and defy other people to explain WHY is alcohol a depressant and caffeine a stimulant? Is that a honest request? I'm afraid you need more than learning your organic chemistry, your biochemistry and your psychopharmacology: you need also learn about intellectual honesty and civil manners...Have a good day.
Iago
> 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
>
>
poster:Iago Camboa
thread:113464
URL: http://www.dr-bob.org/babble/20020725/msgs/114133.html