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

Posted by undopaminergic on July 4, 2008, at 13:36:27

In reply to Re: +++ MAO-A or B ? Gerovital (procaine) selectivity undopaminergic, posted by SLS on July 4, 2008, at 8:18:55

> Clorgyline, a *specific* inhibitor of MAO-A, is a potent antidepressant.

Clorgyline, similarly to selgiline, is subtype selective in low doses.

> 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.

If clorgyline has superior antidepressant efficacy relative to other MAO inhibitors at doses that produce equivalent MAO inhibition, that suggests the existence of additional pharmacological properties of clorgyline.

> 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.

Indeed, considering the incomplete knowledge of the nervous system, a complete understanding of the mechanisms of action of any drug is not feasible.

> 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".

Oral administration of selegiline is somewhat unreliable, considering its variable and extensive first-pass metabolism. Transdermal administration addresses that issue. As I suggested in my previous post, it is likely that the doses of selegiline typically used are more than inadequate in many cases, and although this problem seems to be more common with selegiline, it's by no means unique to it, but has plagued not only clinical use but also research with all the MAOIs - for example, the MAOIs have often erroneously been concluded to be less effective in comparison with TCAs because insufficicent doses were used.




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