Takahata Kazue, Shimazu Seiichiro, Yoneda Fumio
Research Institute, Fujimoto Pharmaceutical Corporation, 1-3-40 Nishiotsuka, Matsubara, Osaka 580-0011, Japan.
Pharmacol Res. 2004 Mar;49(3):253-8. doi: 10.1016/j.phrs.2003.10.005.
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.
使用灌流系统研究了治疗帕金森病的药物(-)-司来吉兰对酪胺诱导的大鼠脑突触体中儿茶酚胺释放的影响。酪胺(10^-7至10^-5M)以剂量依赖的方式增强了前脑和纹状体突触体中[3H]去甲肾上腺素(NA)和[3H]多巴胺(DA)的释放。(-)-司来吉兰(5×10^-5M)对儿茶酚胺的自发释放没有影响,表明它没有类似酪胺的儿茶酚胺释放作用。用(-)-或(+)-司来吉兰(5×10^-5M)预处理可显著阻止酪胺(10^-6M)诱导的NA释放,但不能阻止DA释放。未观察到(-)-司来吉兰对钾(15mM)诱导的NA释放有抑制作用。(-)-司来吉兰的代谢产物(-)-去甲基司来吉兰(5×10^-5M)和单胺氧化酶-A(MAO-A)抑制剂氯吉兰(5×10^-5M)未能阻断酪胺诱导的NA和DA释放。虽然强效DA摄取抑制剂(+)-司来吉兰不抑制酪胺诱导的DA释放,但儿茶酚胺摄取抑制剂诺米芬辛(5×10^-5M)可以抑制。总之,抑制酪胺诱导的NA释放剂量的(-)-司来吉兰对酪胺诱导的DA释放或钾诱导的NA释放没有任何影响。