Posted by SLS on July 4, 2008, at 8:18:55
In reply to Re: +++ MAO-A or B ? Gerovital (procaine) selectivity, posted by undopaminergic on July 4, 2008, at 7:33:29
Excellent post!
> > 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.
COMT is of minor consequence. The intrasynaptic levels of this enzyme are rather small. It would only lead to more background noise were it to be inhibited.
> However, both forms of MAO are responsible for dopamine metabolism,Yes.
> 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.
> 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-
Clorgyline, a *specific* inhibitor of MAO-A, is a potent antidepressant. It probably is more potent than any other MAOI. It is certainly more potent than selegiline. I know for fact that the NIMH department of clinical pharmacology used clorgyline in those people resistant to Nardil and Parnate treatment. No, I have to disagree with you as to the critical role that MAO-A inhibition plays in producing an antidepressant effect. I took clorgyline 15mg myself for several months. It was the only drug that could break through my wall of treatment resistance. I responded well to it, but eventually I reached a plateau that was not acceptable. The NIMH protocol did not allow for additional antidepressants to be used. I think I would have done well with the addition of desipramine or nortriptyline, but my doctor refused to take a risk with a drug that was not approved for marketing. I know I keep saying this, but the NIMH called clorgyline their "ace in the hole". At the time it became no longer available, people who were previously treatment refractory had been in remission for over ten years.
Sometimes you have to look at things clinically rather than theoretically. If it were necessary to understand the mechanism of action of a drug before administering it, no antidepressants would be available.
I feel that selegiline is generally a dud. There are people who respond well to it, but not that many. I followed the development of selegiline from as early as 1983. It was never impressive as an antidepressant in the oral form. Transdermal administration seems to be more effective, but it is no "big gun".
Again, moclobemide can make people feel GEAT, but not without continued dosage escalation. I attribute the MAOI reversibility of this drug to this tachyphylaxis phenomenon and as the cause of this clinical dead end.
- Scott
poster:SLS
thread:836966
URL: http://www.dr-bob.org/babble/20080626/msgs/837956.html