Posted by SLS on August 23, 2001, at 8:02:12
In reply to Re: Moclobemide Miracle, Sal. » SLS, posted by JahL on August 21, 2001, at 10:07:58
Hi JahL.
> > > keep an eye out for another RIMA called befloxatone. I would probably make it my very next choice were it available. I believe Sanofi is pushing it to phase III trials in the US.
> Nice to see you back. Briefly (I know you're not feeling up to much), can you tell me what it is about Befloxatone that excites you so?
I have grown partial to the strategy of inhibiting selectively the MAO-A enzyme to treat severe depression. Clorgyline, an irreversible inhibitor of MAO-A, was the single most impressive antidepressant I have ever been on. Unfortunately, it is no longer manufactured for human consumption. In a conversation I had with William Z. Potter, he suggested that the inhibition of MAO-B might actually be counterproductive when treating depression.
With moclobemide, a reversible inhibitor of MAO-A (RIMA), I experienced a brief antidepressant response that was qualitatively substantially better than those I had experienced with Parnate and Nardil and more similar to that of clorgyline. Unfortunately, within a week, it exacerbated my depression to a degree so horrendous that I remained motionless and curled up into a fetal position, moaning and wimpering for days. It was easily the worst I had ever felt. I have some thoughts as to why this occured, and perhaps why moclobemide rarely seems to "stick". It has been my belief over the last 18 years that alterations in dopaminergic neurotransmission are critically involved in the etiology of my illness (unremitting bipolar II type depression with mania occuring only in association with drug exposure). I found an abstract on Medline that suggests that moclobemide promotes a passive release of dopamine from neuron terminals. This might be the mechanism by which it allows for relapse and exacerbation of depression. I imagine that such a continuous "leakage" of dopamine from the neuron eventually leads to neurotransmitter depletion, especially when such an increase in synaptic dopamine "noise" could further reduce presynaptic vesicular output via negative feed-back inhibition of DA synthesis directed by autoreceptor stimulation. Don't know for sure. However, it seems that this property is idiosyncratic of moclobemide, and is not possessed by the others. If I were God, I would have chosen another RIMA to be marketed before moclobemide. Of course, I would also have chosen to consider the possibility of never having invented depression in the first place. :-)
For me, befloxatone represents the possibility of achieving selective MAO-A inhibition, which I believe is desirable, without promoting dopamine depletion. The question remains whether reversibility equates to reduced efficacy.
- Scott
poster:SLS
thread:75749
URL: http://www.dr-bob.org/babble/20010822/msgs/76098.html