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Re: combining nardil and selegiline

Posted by SLS on August 15, 2008, at 4:45:48

In reply to Re: combining nardil and selegiline, posted by Sigismund on August 14, 2008, at 23:21:36

> Does selegeline have any effect on substances that affect GABA?
>
> Someone once said something about that, but I forget what.

Nardil most definitely increases GABAergic neurotransmission. It does this through inhibiting the enzyme that manufactures GABA - GABA transaminase. In this regard, it is works on GABA much like an MAOI does for the monoamines. My guess is that this is why Nardil has antianxiety properties that Parnate lacks.

I am not inclined to recommend adding oral selegiline at dosages higher than 5mg when combining it with Nardil. Nardil already sufficiently blocks MAO-A and MAO-B at therapeutic dosages (60-90mg). However, there are properties of selegiline and its metabolites other than MAO inhibition that tend to be energizing at low dosages.

I would wait until you get more feedback regarding your proposed treatment plan. I tend to be very cautious when working with MAOIs, even though I am presently combining Nardil and nortriptyline. Perhaps you could titrate the selegiline very slowly if 5mg doesn't produce results. The thing about the oral preparation is that most of selegiline is metabolized to amphetamine-like compounds.

http://dmd.aspetjournals.org/cgi/content/full/25/6/657

"Nine urinary metabolites of selegiline hydrochloride [N-methyl-N-propargyl(2-phenyl-1-methyl)ethylammonium chloride], a monoamine oxidase inhibitor, after administration to humans were identified. Their identities were confirmed by comparison of the spectra from GC/MS of peaks with those of authentic compounds. The following metabolites and unchanged drug (selegiline) were detected in urine: (R)-desmethylselegiline, (R)-methamphetamine, (R)-amphetamine, (1S,2R)-norephedrine, (1R,2R)-norpseudoephedrine, (1S,2R)-ephedrine, (1R,2R)-pseudoephedrine, (R)-p-hydroxyamphetamine, and (R)-p-hydroxymethamphetamine. The metabolites excreted 2 days after administration of 2.5-10 mg of selegiline hydrochloride amounted to 44-58% of the dose. Selegiline was metabolized by three distinct pathways: N-dealkylation, beta -carbon hydroxylation, and ring-hydroxylation. The major metabolite was (R)-methamphetamine. During metabolism, no racemic transformation occurred and beta -carbon hydroxylation showed apparently product stereoselectivity."

While I have no problem with adding an amphetamine, I am concerned that at higher dosages, selegiline will produce a shotgun blast of stimulant compounds that will challenge the Nardil. This is why I recommend not exceeding 5mg to start with.


- Scott

 

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