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Re: Beta Receptor Down-Regulation

Posted by PeterJ on April 26, 2000, at 1:57:52

In reply to Re: Beta Receptor Down-Regulation, posted by Scott L. Schofield on April 25, 2000, at 23:11:41

> > One antidepressant which still produces beta receptor down- regulation in serotonin lesioned animals is clorgyline. It is hypothesized that clorgyline has such a powerful effect on serotonin levels that it overcomes the effect of the lesions of the sertonin system.
> Q: What is the proposed mechanism here? Are these chemical lesions? Do these lesions interfere with vesicular release, but spare postsynaptic processes? Is serotonin released passively from serotonergic nerve terminals? Does this serotonin stimulate nerves along the lesioned pathway to fire via local synapses, or does it migrate interstitially to remote sites?

The lesions are produced by 5,7-dihydroxytryptamine which destroys serotonergic axons.
It is believed that clorgyline boosts the remaining levels of serotonin, but it is not
kown for sure if this is due to a small number of surviving axons or due to diffusion
of serotonin from other sites.

> I took clorgyline for about a year through an IND protocol administered by the NIMH of the National Institutes of Health. It is an amazing drug. It is arguably the most effective antidepressant in the world, and certainly the most potent MAO-inhibitor. Dr. William Potter and his colleagues considered it to be their "ace-in-the-hole" when treating refractory cases. As monotherapy, I found that it exerted the strongest persistant antidepressant effect of any drug I have taken. Unfortunately, I was only partially responsive, and was not permitted to combine it with anything else as per the protocol. My doctor was understandably reluctant to add desipramine, which I considered to be my best prospect. I wish I had forced the issue.
> Clorgyline was never available as a pharmaceutical anywhere in the world. I don't know why. It had two things going for it as an antidepressant for treatment-resistant cases. It is extremely selective for MAO-A and it is irreversible. I spoke to a couple of doctors at the NIMH last week regarding its availability. I wanted to use it again and twist my doctor's arm to augment it with other antidepressants. Who knows, maybe having Lamictal on-board would have done the trick. I was informed that the chemical company that manufactures clorgyline no longer produces a preparation for human consumption. The three people who had been maintained on it for over a decade were forced to discontinue it. It remains available for animal experiments.
> Crap.
> The previous word is a very poor expletive for conveying excruciatingly painful emotions. I am very afraid.
> - Scott

Your frustration is understandable. There ought to be some kind of
provision that allows people who have not responded to standard
medications access to experimental chemicals. I am sure you
would be willing to sign a waiver saying the responsiblity
was yours if you could only try it. The situation now is...
well, you put it best...crap.





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