Posted by Questionmark on April 28, 2008, at 10:40:20
In reply to Re: Parnate metabolites, posted by undopaminergic on March 30, 2008, at 18:15:46
Well said; great points.
> Most attempts to investigate the metabolism of tranylcypromine in humans have failed to detect amphetmines as metabolites. However, it appears that the studies have included only a very small number of subjects, and that the doses used have been rather low. It is possible that a massive dose would result in intestinal and hepatic concentrations of tranylcypromine that are sufficient to activate metabolic pathways that are not involved in the breakdown of the drug at low concentrations. Furthermore, differences in digestive flora (bacteria, fungi) may result in differences in the range of compounds formed from the same starting material in different individuals.
>
> On the other hand, amphetamines as tranylcypromine metabolites may well be only a myth that is sufficiently plausible so as not to be easily dismissed.
>
> There are also alternative hypothetical explanations for the apparently unique properties of tranylcypromine (as a particularly addictive antidepressant, etc.). For example, the stimulant effects may result not from amphetamines, but from other active metabolites or from tranylcypromine itself. I don't know if it has been investigated, but tranylcypromine might function as a dopamine (or multiple monoamine) reuptake inhibitor (like cocaine and methylphenidate) or neurotransmitter-releasing agent (like amphetamine). Such effects may become pronounced only at high doses, which may explain the lack of stimulant-like properties of the drug at low doses.
>
> As to toxicity, even if data from rats were applicable to humans, one can't compare data on acute toxicity, such as a single massive dose in a tranylcypromine-naive animal, to a case of slow titration over a long period of time. Not even the data from cases of overdose in humans are necessarily applicable, as they generally describe situations of a drastic, large and sudden increase in dose (suicide attempts, etc.). Chronic toxicity is relevant, but there is not much information available on the long-term effects of tranylcypromine or other MAOIs, except anecdotal reports of apparent safe and effective use. It is more than likely that, by slow titration, one may surpass doses that would be lethal to a trancylcypromine-naive individual - as an exmaple, here is a report of a daily dose of 440 mg:
> http://www.ncbi.nlm.nih.gov/pubmed/1873639
>
> Anyway, even if the body is given time to adjust to ever increasing doses of tranylcypromine, the increases must eventually come to an end - in one way or the other. At this time, the factors that ultimately limit dose escalation do not seem well (if at all) defined, so it is up to adventurous users to explore them, and hopefully document and publish their findings.
poster:Questionmark
thread:819514
URL: http://www.dr-bob.org/babble/neuro/20080418/msgs/826038.html