Posted by Scott L. Schofield on April 25, 2000, at 23:11:41
In reply to Beta Receptor Down-Regulation, posted by PeterJ on April 25, 2000, at 3:44:51
Dear Peter,
You couldn't possibly be more wrong. :-)> (I am sure Scott knows all this, but it's an interesting topic.)
I didn't. But I do now. Thank you for this wonderfully lucid explanation.
> 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?
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
poster:Scott L. Schofield
thread:30864
URL: http://www.dr-bob.org/babble/20000420/msgs/31293.html