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Re: +++ MAO-A or B ? Gerovital (procaine) selectivity

Posted by undopaminergic on July 4, 2008, at 7:33:29

In reply to Re: +++ MAO-A or B ? Gerovital (procaine) selectivity Marty, posted by SLS on July 3, 2008, at 5:34:15

> I feel strongly that MAO-A is the main player in mood disorders.
>

Maybe, and it is certainly true to the extent that reducing serotonin metabolism is of importance. MAO-A also deaminates noradrenaline and adrenaline, in contrast to MAO-B, but in competition with COMT.

However, both forms of MAO are responsible for dopamine metabolism, and the B form seems to be the major factor in the extracellular space in most regions of the brain - including the striatum and nucleus accumbens. To the extent that reduced breakdown of trace amines (TAs) is of importance in the antidepressive effect of MAOIs, the B form of MAO is also the major - or exclusive - factor for some of the TAs, including phenylethylamine (PEA).

Furthermore, because the complete inhibition of MAO-B is associated with very few side effects, it seems the best place to start in the quest to achieve the critical level of total MAO-inhibition required to produce a robust antidepressive response. Meanwhile, MAO-A inhibition has several adverse effects, including tyramine sensitivity and the downregulation of neurotransmitter synthesis in response to inhibition of intracellular MAO-A.

It would be desirable to also inhibit COMT, an enzyme greatly contributing to extracellular destruction of all the cathecolamines, but unfortunately, the only central COMT inhibitor, tolcapone, has turned out to be rather hepatoxic.

Regarding genes, reduced MAO-B activity has been associated with a diminished risk of Parkinson's disease, while reduced MAO-A activity is related to antisocial behaviour. In other words, reducing MAO-B activity seems more unambiguously beneficial.

>
> Moclobemide is a great example of how a selective inhibitor of MAO-A can produce a robust remission of depression, even if only transiently.
>

On the other hand, at least some people report subtype selective doses of selegiline to be more antidepressive than subtype selective doses of moclobemide. (Of the two, I've only tried selegiline, and I found its antidepressive effect to be transient.)

> Selegiline does not seem to be nearly as potent as Nardil or Parnate when treating severe depression, as the reported experiences on PB give an indicator to.
>

That is probably dose-dependent. Few people seem to use more than modest doses of selegiline - such as the 12 mg patch. Meanwhile, doses of 100 mg or even more of Nardil and Parnate are not uncommon.

> My guess is that there is indeed some MAO-A inhibition with selegiline at the dosages necessary to treat depression.
>

Although small doses may be sufficient in rare cases, I think your guess is correct.

> Investigators warn of this when discussing hypertensive crisis, such that it is recommended to not ingest tyramine at any dosage above the minimum of 6mg/24hr. This would be an indicator that selegiline inhibits MAO-A in the gut.
>

It appears that the 12 mg patch may sufficiently inhibit MAO-A in the gut to create a risk of tyramine related hypertensive crisis, but only in some people. In some trials of the 12 mg patch there were no dietary restrictions observed, but no hypertensive complications were reported. However, in tyramine sensitivity tests, a few of of those treated with the 12 mg patch, were found to be sufficiently senstitive to be at risk.


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