Jackson E A, Neumeyer J L, Kelly P H
Eur J Pharmacol. 1983 Jan 28;87(1):15-23. doi: 10.1016/0014-2999(83)90045-6.
The behavioral actions of some novel aporphines have been examined in rats with selective unilateral 6-hydroxydopamine (6OHDA)-induced destruction of nigrostriatal dopaminergic neurons, and in rats with bilateral 6OHDA-induced destruction of mesolimbic dopaminergic neurons. Dopaminomimetics such as apomorphine (APO) in these animal models elicit circling behavior and locomotor activity respectively. In animals with unilateral nigrostriatal lesions (-)-2,10,11-trihydroxy-N-n-propylnoraporphine (TNPA) and (-)-10,11-methylenedioxy-N-n-propylnoraporphine (MDO-NPA) elicited weak, but prolonged, contraversive circling, whereas (-)-2,10,11-trihydroxyaporphine (2-OH.APO) was inactive. In animals with bilateral destruction of mesolimbic dopaminergic neurons TNPA and MDO-NPA elicited a strong stimulation of locomotor activity, while 2-OH.APO was inactive. The results suggest that TNPA and MDO-NPA, but not 2-OH.APO, exert central dopaminomimetic effects in vivo. The results are also consistent with previous data indicating that N-propyl substitution of aporphines causes a relative enhancement of activity in animal models which emphasise effects at mesolimbic rather than striatal dopaminergic receptors.
已在选择性单侧6-羟基多巴胺（6OHDA）诱导黑质纹状体多巴胺能神经元破坏的大鼠以及双侧6OHDA诱导中脑边缘多巴胺能神经元破坏的大鼠中研究了一些新型阿朴啡的行为作用。在这些动物模型中，多巴胺模拟物如阿扑吗啡（APO）分别引发转圈行为和运动活性。在单侧黑质纹状体损伤的动物中，（-）-2,10,11-三羟基-N-正丙基去甲阿朴啡（TNPA）和（-）-10,11-亚甲二氧基-N-正丙基去甲阿朴啡（MDO-NPA）引发微弱但持续的向对侧转圈，而（-）-2,10,11-三羟基阿朴啡（2-OH.APO）无活性。在中脑边缘多巴胺能神经元双侧破坏的动物中，TNPA和MDO-NPA引发强烈的运动活性刺激，而2-OH.APO无活性。结果表明，TNPA和MDO-NPA而非2-OH.APO在体内发挥中枢多巴胺模拟作用。这些结果也与先前的数据一致，表明阿朴啡的N-丙基取代在强调对中脑边缘而非纹状体多巴胺能受体作用的动物模型中导致活性相对增强。
