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Re: Nardil and GABA

Posted by Adam on December 8, 1999, at 22:35:08

In reply to Nardil and GABA, posted by Elizabeth on December 8, 1999, at 19:19:28

> Hey everybody.
> Nardil, or one of its metabolites rather, is known to increase brain GABA concentrations by inhibiting GABA transaminase. This is believed to be related to its hydrazine structure, but I can't find any information on whether Marplan (also a hydrazine derivative) does this as well. I'm wondering if anybody knows the exact mechanism. For some reason I'm thinking it has to do with pyridoxal phosphate (i.e., vitamin B6) depletion (like, the metabolite forms a complex with p5p that inhibits GABA-T) but I have no idea where I might have read that (can't find anything about it anywhere). Anybody know more?

The metabolite(s) of phelzine that inhibit GABA transaminase is unkown, but is dependant on MAO-B metabolism for
production (read about this a while ago). I found something once that suggested clozapine and isocarboxazid increase
GABA by dysregulation of GABA release via GABA(A) receptor binding. I think something like that was suggested for
phenelzine also in the reference where they determined MAO-B was most important. I can't remember why.

As for the mechanisms of hydrazine analog action on GABA transaminase, check out the following:

Binding and reactivation kinetics suggests hydrazine action is not due to depletion of a cofactor, but rather the
dissociation of the cofactor from the enzyme.

Hope this is helpful.




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