Marek G J, Vosmer G, Seiden L S
University of Chicago, Department of Pharmacological Science, IL 60637.
Pharmacol Biochem Behav. 1990 May;36(1):187-90. doi: 10.1016/0091-3057(90)90147-a.
Neostriatal 6-hydroxydopamine (6-OHDA) was detected in 6 of 13 rats pretreated 2 or 4 hr earlier with methamphetamine (MA; 100 mg/kg, SC) and pargyline (25 mg/kg, IP, 30 min before MA injection). Neostriatal 6-OHDA was detected in 2 of 16 rats treated 2 or 4 hr earlier with MA. These results suggest that pargyline pretreatment may enhance formation of 6-OHDA from endogenous stores of dopamine (DA) following MA administration. Alternatively, these results suggest that pargyline pretreatment may protect endogenously formed 6-OHDA from oxidative deamination by monoamine oxidase. Enhancement of MA-induced neostriatal 6-OHDA levels may be the mechanism by which pargyline enhances the long-term neurotoxic effects of MA upon dopaminergic nerve terminals. These observations support the hypothesis that MA toxicity to DA-containing fibers is caused by the conversion of released DA into 6-OHDA.
在13只于2或4小时前接受甲基苯丙胺（MA；100毫克/千克，皮下注射）和帕吉林（25毫克/千克，腹腔注射，在MA注射前30分钟）预处理的大鼠中，有6只检测到新纹状体6-羟基多巴胺（6-OHDA）。在16只于2或4小时前接受MA处理的大鼠中，有2只检测到新纹状体6-OHDA。这些结果表明，帕吉林预处理可能会增强MA给药后多巴胺（DA）内源性储存形成6-OHDA的过程。或者，这些结果表明，帕吉林预处理可能会保护内源性形成的6-OHDA不被单胺氧化酶氧化脱氨。MA诱导的新纹状体6-OHDA水平升高可能是帕吉林增强MA对多巴胺能神经末梢长期神经毒性作用的机制。这些观察结果支持了以下假设，即MA对含DA纤维的毒性是由释放的DA转化为6-OHDA所致。
