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Re: Help..severe anger.... SLS

Posted by undopaminergic on September 17, 2021, at 8:22:53

In reply to Re: Help..severe anger.... undopaminergic, posted by SLS on September 17, 2021, at 3:45:40

> >
> > 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.
> I'm sure there is a biological reason for why we see this.

My best theory is as follows: MAO-B has been called phenylethylaminase, because its primary substrate is phenylethylamine (PEA), which at higher concentrations works like amphetamine. Thus PEA releases dopamine (and noradrenaline and maybe serotonin) from dopaminergic nerve terminals. This may result in a sensitation of dopamine autoreceptors, reducing dopamine synthesis and release. This may result in a functional depressive (apathetic, etc.) effect. So I wonder whether adding sulpiride or amisulpride would help.

But: PEA administered during MAO-B inhibition in sufficient quantities yields a powerful antidepressant (or stimulant) effect.

> Selegiline (including EMSAM) does not exert antidepressant effects until the dosage is high enough to lose its selectivity. Both MAO-A and MAO-B become inhibited, yet this drug sucks as an antidepressant. By comparison, the reversible inhibitor of MAO-A (RIMA), moclobemide, produces an antidepressant far more robust than selegiline. Unfortunately, the improvement is farily brief. My guess is that reversibility is a liability. Moclobemide yields a progressive dosage escalation and ultimate failure. In my experience, moclobemide is more anhedonic and motivating than tranylcypromine while it lasts. I was always under the impression that Nardil inhibits more MAO-A than tranylcycpromine does. Maybe you can look into that. I'm a little short on time.

I don't feel this is important enough to spend much time investigating. It is an interesting curiosity. I wouldn't say moclobemide is necessarily a better antidepressant than EMSAM, but I don't have experience with this. You could be right.

> Psychiatry: So many questions. So few answers.






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