Posted by SLS on October 1, 2022, at 20:12:13
In reply to Re: Clorgyline is a MAOI specific for MAO-A. » SLS, posted by undopaminergic on September 30, 2022, at 6:28:50
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> > As far as the necessity to block both MAO subtypes to treat depression, I haven't come across anything that would lead me to believe that an antidepressant response requires that MAO-B be inhibited. In fact, selegiline and clorgyline demonstrate the reverse. I like to mention clorgyline because it is specific for MAO-A. It doesn't affect MAO-B at all. So, for a bunch of treatment resistant cases of depression, the NIH provided clorgyline for people who responded to nothing else. Many of these patients went home happy for the first time. As the doctors at NIH liked to say, "Clorgyline is our ace-in-the-hole."
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> But why is clorgyline more effective than nonselective MAOIs? Does it have other mechanisms of action in addition to MAO-A inhibition, or is inhibiting MAO-B a negative thing when treating depression?I don't know. Your guess is as good as mine. Sometimes, I just pay attention to what works without worrying about how it works. That's what doctors have been doing since 1957 (unfortunately).
Maybe you don't need any MAO-B inhibition at all to treat depression. There is evidence that you can effectively treat depression with compounds that are specific to MAO-A. The two examples I have in mind are clorgyline (irreversible) and moclobemide (reversible). I can' think of a single selective inhibitor of MAO-B that is effective in depression. Pargyline is selective for MAO-B, but not specific. It disappeared decades ago.
https://www.nature.com/articles/s12276-021-00646-3
> Why did you stop using it?
I was supplied with clorgyline by the NIH. That was part of the bargain. Clorgyline was discovered and manufactured for many years as a biological probe for neuroscience investigations. It was never approved. Perhaps no one became interested because the patent had expired. I don't know. The NIH had been using clorgyline for quite a few years before I got there. Having been aware of clorgyline for 10 years, I was quick to sign up for their research patient program. Clorgyline was what the NIH used to treat patients who responded to nothing else. I received my supply through the mail, I think. It worked for me more than any other single drug had. The problem was, the head of research department wouldn't let me add a tricyclic to it. I absolutely must have both in order to respond.
The reason I stopped taking clorgyline was because the partial improvement without a tricyclic was not sufficient for me. A few years passed when I found out that the NIH were no longer using clorgyline, and required that all of their former patients, most of whom were in remission, stop taking it. They became concerned when a number of adverse cardiac events were reported. My only thought is that clorgyline might be capable of producing cardiac valvulopathy. This was the case with fenfluramine, which is a potent serotonin (5-HT) releaser. Remember Fen-Phen?
- ScottSome see things as they are and ask why.
I dream of things that never were and ask why not.The only thing necessary for the triumph of evil is that good men do nothing.
poster:SLS
thread:1120765
URL: http://www.dr-bob.org/babble/20220917/msgs/1120830.html