(−)-Deprenyl inhibits tyramine-induced noradrenaline release, but not tyramine-induced dopamine release or potassium-induced noradrenaline release, from rat brain synaptosomes

Abstract

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 [ 3 H] noradrenaline (NA) and [ 3 H] dopamine (DA) from forebrain and striatal synaptosomes in a dose-dependent manner. (−)-Deprenyl (5×10 −5 M) had no effect on spontaneous catecholamine release, suggesting that it has no tyramine-like catecholamine releasing effect. Pretreatment with (−)- or (+)-deprenyl (5×10 −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 (15 mM)-induced NA release. (−)-Desmethyldeprenyl (5×10 −5 M), a metabolite of (−)-deprenyl, and a monoamine oxidase-A (MAO-A) inhibitor, clorgyline (5×10 −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 (5×10 −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.