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Re: Judy -- Selegiline, Pindolol, Melatonin & Estrogen

Posted by Adam on January 4, 2000, at 11:10:32

In reply to Re: Judy -- Selegiline, Pindolol, Melatonin & Estrogen, posted by Judy on January 3, 2000, at 12:47:50

A couple of salient points (perhaps):

Melatonin: I have considered using melatonin to help with what appears to be selegiline-induced insomnia and sleep-cycle disturbance. I had some concern about this combination because melatonin is a seratonin derivative, concerns that seem to be legitimate based on a bad experience Elizabeth had combining mel. with an MAOI. However, I have been able to find no mechanistic basis for melatonin-induced seratonin syndrome. Recently I spoke with my doctor about such a combo, and he also felt this was a bad idea, though he admitted he could provide no rationale beyond what I stated above. Just FYI.

On selegiline and exogenous sex hormones: Before you combine selegiline and estrogen treatment, please consider the following (I came across it a while ago when searching for info. on selegiline metabolism):

Br J Clin Pharmacol 1999 Mar;47(3):249-54

Dose linearity study of selegiline pharmacokinetics after oral administration: evidence for strong drug interaction with female sex steroids.

Laine K, Anttila M, Helminen A, Karnani H, Huupponen R
Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.

AIMS: The purpose of this study was to characterize the dose relationship of selegline and desmethylselegiline pharmacokinetics within the selegiline dose range from 5 to 40 mg. METHODS: Eight female subjects, of whom four were using oral contraceptives, ingested a single dose of 5 mg, 10 mg, 20 mg or 40 mg of selegiline HCl in an open four-period randomized study. Concentrations of selegiline and desmethlylselegiline in serum were measured by gas chromatography for 5 h. As it became evident that the use of oral steroids had a drastic effect on selegiline concentrations, the pharmacokinetic analyses were performed separately for oral contraceptive users and those not receiving any concomitant medication. RESULTS: The total AUC and Cmax of selegiline were 10-to 20-fold higher in those subjects taking oral steroids compared with subjects with no concomitant medication; this finding was consistent and statistically significant at all the four dose levels. The dose linearity of selegiline pharmacokinetics failed to be demonstrated in both groups. The AUC and Cmax of desmethylselegiline were only moderately higher (about 1.5-fold; P=NS at each dose level) in the subjects taking oral steroids than in those not receiving concomitant medication. The AUC values of desmethylselegiline increased in a dose linear manner in subjects with no concomitant medication, but not in the oral steroid group. The metabolic ratio (AUC(desmethylselegiline)/AUC(selegiline)) was several-fold lower in the group receiving oral steroids compared with the no-concomitant-medication group (P Thanks to your all for your advice/suggestions/theories. My doctor has finally returned from vacation and I'm awaiting a return call from him today.
> Selegiline didn't see me through the holidays very well on its own. I'm not sure if augmenting it will do the trick, but I'd sure like to give it a try before trashing it. I've also made an appointment for a full physical and will ask for thorough thyroid and estrogen levels and anything else they want to check.
> Rick - does Melatonin need to build up in one's system or is it a quick-in/quick-out drug like a sleeping pill would be?
> Thanks again, all. Judy




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