(-)-Deprenyl inhibits tyramine-induced noradrenaline release, but not tyramine-induced dopamine release or potassium-induced noradrenaline release, from rat brain synaptosomes.
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.
Takahata
Kazue
K
Research Institute, Fujimoto Pharmaceutical Corporation, 1-3-40 Nishiotsuka, Matsubara, Osaka 580-0011, Japan.
Shimazu
Seiichiro
S
Yoneda
Fumio
F
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014439:Tyramine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D012642:Selegiline; D011188:Potassium; D004298:Dopamine; D009638:Norepinephrine; D014439:Tyramine