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Re: Help..severe anger.... » SLS

Posted by undopaminergic on September 16, 2021, at 13:08:18

In reply to Re: Help..severe anger.... » undopaminergic, posted by SLS on September 16, 2021, at 12:26:00

> >
> > Why would clorgyline be more effective than the non-selective MAOIs? Is MAO-B inhibition harmful to the treatment of depression?
>
> That's a really good question. I don't know the answer to it. I'm guessing that you are referring to a scenario similar to that of citalopram and escitalopram?
>

I hadn't thought of it like that, but I guess there is an analogy. Just to clarify, I'm wondering why specific MAO-A inhibition with clorgyline would be better than dual MAO-A and MAO-B inhibition with classic MAOIs. MAO-B contributes to dopamine breakdown, so one would think that inhibiting it in addition to MAO-A would be beneficial, rather than the opposite, that is MAO-B inhibition being detrimental.

> A long time ago, I read that Parnate (tranylcypromine) is actually partially reversible.
>

I seem to recall that it is *slowly* reversible. So slowly that it is negligible in practice. Also, I've read that tranylcypromine is slightly selective for MAO-B.

> I found this, but one has to assume that the pharmacological effect being referred to is MAO inhibition. I imagine it is, but I don't see how this would be of consequence.
>
> "However, recent research has demonstrated that tranylcypromine can produce direct and reversible pharmacologic effects"
>
> https://pubmed.ncbi.nlm.nih.gov/1813896/

No, at least as I understand it, they are speaking specifically about non-MAOI actions of tranylcypromine -- that would be, for example, the amphetaminergic action. MAO inhibition, because it is so slowly reversible, does not require tranylcypromine to be continuously present in tissues. Other pharmacodynamical actions, that are readily reversible, do require certain concentrations of the drug. Therefore, the pharmacokinetics (ie. clearance) of the MAOI compound itself are of interest even though it is irrelevant to the maintenance of MAO inhibition.

-undopaminergic


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