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Re: ANYONE ON SELEGELINE? QUESTIONS... SLS

Posted by hok on February 16, 2003, at 12:53:03

In reply to Re: ANYONE ON SELEGELINE? QUESTIONS..., posted by SLS on February 16, 2003, at 10:46:48

Scott-

Interesting synopsis. Thanks for the info.
I am currently deciding whether to try use the selegiline tablets or the subligual form as an augmentor. Until this point, I assumed the sublingual form was the obvious choice since it bypasses the 1) GI tract, 2) keeps more of the active form in the bloodstream and less of its metabolites floating around -- so hopefully less side effects. But your theory on the antidepressant effects being due to the methamphetamine metabolite instead of the MAO-B inhibitory effect makes me think I should try the tablet form. On a side note, I've been a smoker in the past, and I always believed that the strong anti-anhednonic effect I've always gotten from it was due to the MAO-B inhibition involved.

Have a couple of questions, if you don't mind. Would like to hear more of your thought on the biochemical details of the atypical/anhedonia issue if possible, and what implications this has for taking either form of the drug.

Also, what is the downside of the sublingual form? Does its pharmacokinetics fade very fast so frequent dosing is needed? Besides not having to administrate multiple doses throughout the day, what will be tha advantage of the patch over the sublingual form?

And lastly, have you had experience with either one personally? If so, can you relate your conclusions to us all? It would be much appreciated.

Thanks,

HK


> Hi.
>
> Selegiline, once called l-deprenyl, was initially researched and developed as an antidepressant. Quite a bit of money was poured into getting it approved as such. Selegiline is different from the other irreversible MAOIs (Parnate, Marplan, and Nardil) in that it binds to the MAO-B form of monoamine-oxidase much more strongly than it does to MAO-A. MAO-B metabolizes dopamine (DA). MAO-A metabolizes both norepinephrine (NE) and serotonin (5-HT). At low dosages, it was found that selegiline was selective for the MAO-B enzyme. Generally speaking, it is the MAO-A enzyme that seems to be the more important when treating depression.
>
> Selegiline is *selective*, but not *specific*. At dosages above 10mg, selegiline begins to inhibits MAO-A in addition to MAO-B. At the low dosages used initially, it proved to be a disappointment. However, it was subsequently studied to evaluate its utility in treating Parkinsons Disease , a disorder involving the degeneration of neurons that utilize dopamine as their neurotransmitter. Selegiline demonstrated enough efficacy to be approved by the FDA for Parkinsons, but not depression.
>
> In order to work as an antidepressant monotherapeutically in severe depression, it seems that the dosage of selegiline must be greater than 10mg per day. No longer being selective, it inhibits both MAO enzymes similar to Parnate and Nardil. At the point where MAO-A becomes significantly inhibited, the same dietary restrictions that must be followed for Parnate and Nardil apply with selegiline as well. This is true for oral administration. However, when used as a patch (transdermal delivery), the MAO-A along the digestive tract is bypassed, preventing the hypertensive food-reaction. Another advantage of the transdermal patch is that it maintains a constant blood level of selegiline throughout the day. People often report that the quality of their antidepressant response is significantly better and qualitatively different than that they experience with oral selegiline.
>
> Selegiline can make a good augmentor of standard antidepressants. It can do so at dosages lower than what are necessary for its use as monotherapy. On Psycho-Babble, I see quite a few people report success using 5.0mg of selegiline in this fashion. Low dosages might also be effective for dysthymia, ADD / ADHD, chronic fatigue syndrome, and perhaps Alzheimers Dementia. My guess is that the reason low dosages of selegiline are effective for the former three is that it is metabolized into methamphetamine in the body, and that it methamphetamine that produces the improvements in mood, energy, and attentional deficits.
>
> I forgot what the question was. :-)
>
>
> - Scott


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poster:hok thread:200506
URL: http://www.dr-bob.org/babble/20030214/msgs/200905.html