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Re: High doses of Parnate Steeler Tookahn

Posted by SLS on October 22, 2000, at 11:19:16

In reply to Re: High doses of Parnate, posted by Steeler Tookahn on October 22, 2000, at 8:45:37

Dear Steeler,

> Thanks very much Scott,
> I'm glad to get an idea of the kind of doses people are using these days. I read Jay Amsterdam's paper on high doses of Parnate.
> I'm also glad to see people using TCAs with MAOIs. I've tried practically everything as an adjunct with little success. A tri-cyclic may be in the future.

> >I have come across some research studies that indicate that Parnate begins to do things at high dosages that it does not do at lower dosages that are unrelated to MAO inhibition. One such effect is the downregulation of 5-HT2 receptors, something that occurs with several other antidepressants. Unlike Nardil, Parnate has been shown to produce a decrease in dopamine D2 receptor densities.

> Scott -could you elaborate on what this downregualtion might mean to the patient.

No. The best I can do is offer associations between the observations made in lab experiments. I think this is pretty much where things are at right now. For example, before the age of SSRIs, it was thought to be necessary that an antidepressant exert a direct effect at NE neurons and produce a downregulation of postsynaptic NE beta-1 (and not beta-2) receptors. The time course of this downregulation is observed to occur about two weeks from initial exposure to the drug. This, of course, seems to mirror the time course of the onset of clinical antidepressant activity. Well, guess what? SSRIs, without directly affecting the NE nerve synapse (at least not that has yet been observed, to my knowledge), somehow produces a downregulation of NE beta-1 receptors that takes two weeks occur. This is nothing more than an association of observations for which there is not yet an adequate understanding. It looks pretty important, though. But where does it fit into the explanation of what causes depression and how to treat it?

I know I sound like a broken record, but, "We are not there yet."

> My knowledge of neurobiology (as well as my Neurobiology itself) is not what it used to be.

What did it used to be? I am perpetually amazed at the level of knowledge and understanding that Babblers possess without having a formal education in the field. I have none.

> I don't think I could tell an Axon from a Dendrite without a microscope (that's an attempt at humor).

:-) Thanks for the tip-off. The way I am feeling this morning, I doubt I could distinguish comedy from trajedy. Actually, I think we all do a pretty good job of combining the two. For me, it is a survival strategy. By the way, what's a dendrite? (That's an attempt at humor too).

Nice talking to you.

- Scott




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