Posted by SLS on October 31, 2006, at 9:12:14
In reply to Re: Trying Emsam. » linkadge, posted by zeugma on October 30, 2006, at 16:06:38
> I would think transdermal selegiline, compared to the oral route, would have a much more delayed effect, because most of selegiline's immediate effect is mediated through its amphetamine metabolites and the patch increases the parent-to-metabolite ratio.
The parent compound might have stimulant effects of its own.
I found a few abstracts that hint at this.
This would help explain the acute energizing effect that appears within the first few days of initiating Emsam treatment as reported by people here on Psycho-Babble. It may indicate that selegiline is actually more potent as a releaser of DA and NE than are its metabolites and explains why the transdermal delivery system produces a greater energizing effect that does the oral preparation.
I subsequently found another abstract that demonstrated an inhibitory effect for tyramine-induced release of NE, but not for DA by Emsam, perhaps an index of reuptake inhibition. This might indicate a greater energizing effect than reward/hedonic effect by Emsam during the first few weeks of treatment. So far, this is consistent with what has been reported here.
- Scott
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Neurobiology (Bp). 2000;8(2):179-99. Related Articles, Links(-)Deprenyl (Selegiline): past, present and future.
Knoll J.
Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.
(-)Deprenyl (Selegiline), the N-propargyl analogue of (-)methamphetamine, is the only drug in clinical case which, by enhancing the impulse propagation mediated release of noradrenaline and dopamine in the brain (catecholaminergic activity enhancer, CAE, effect), keeps in small doses without side-effects the catecholaminergic brain system on a higher activity level. (-)Deprenyl stimulates the catecholaminergic neurons selectively in the brain because, in contrast to PEA and the amphetamines which induce the continuous release of noradrenaline and dopamine from their intraneuronal stores, (-)deprenyl is devoid of this property. It is due to the CAE effect that a) the maintenance of rats on (-)deprenyl during the postdevelopmental phase of their life slows the age-related decline of sexual and learning performances and prolongs life significantly; b) patients with early, untreated Parkinson's disease maintained on (-)deprenyl need levodopa significantly later than their placebo-treated peers, and when on levodopa plus (-)deprenyl, they live significantly longer than patients on levodopa alone; and c) in patients with moderately severe impairment from Alzheimer's disease, treatment with (-)deprenyl slows the progression of the disease. It is reasonable to expect that a prophylactic low dose administration of a safe catecholaminergic activity enhancer substance during the postdevelopmental phase of life will slow the age-related decline of behavioral performances, delay natural death and decrease susceptibility to Parkinson's disease and Alzheimer's disease.
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Pharmacol Res. 2004 Mar;49(3):253-8. Related Articles, Links
Click here to read
(-)-Deprenyl inhibits tyramine-induced noradrenaline release, but not tyramine-induced dopamine release or potassium-induced noradrenaline release, from rat brain synaptosomes.Takahata K, Shimazu S, Yoneda F.
Research Institute, Fujimoto Pharmaceutical Corporation, 1-3-40 Nishiotsuka, Matsubara, Osaka 580-0011, Japan.
The effect of (-)-deprenyl (selegiline), a therapeutic agent for Parkinson's disease, on the tyramine-induced release of catecholamine from rat brain synaptosomes was studied using a superfusion system. Tyramine (10(-7) to 10(-5)M) enhanced the release of [3H]noradrenaline (NA) and [3H]dopamine (DA) from forebrain and striatal synaptosomes in a dose-dependent manner. (-)-Deprenyl (5x10(-5)M) had no effect on spontaneous catecholamine release, suggesting that it has no tyramine-like catecholamine releasing effect. Pretreatment with (-)- or (+)-deprenyl (5x10(-5)M) significantly prevented the tyramine (10(-6)M)-induced NA release, but not DA release. The inhibitory action of (-)-deprenyl was not observed on potassium (15mM)-induced NA release. (-)-Desmethyldeprenyl (5x10(-5)M), a metabolite of (-)-deprenyl, and a monoamine oxidase-A (MAO-A) inhibitor, clorgyline (5x10(-5)M), failed to block the tyramine-induced NA and DA release. Although (+)-deprenyl, a potent DA uptake inhibitor, did not inhibit tyramine-induced DA release, a catecholamine uptake inhibitor nomifensine (5x10(-5)M) did. In summary, (-)-deprenyl at a dose inhibiting tyramine-induced NA release did not have any effect on tyramine-induced DA release or potassium-induced NA release.
PMID: 14726221 [PubMed - indexed for MEDLINE]
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