Löschmann P A, Smith L A, Lange K W, Jähnig P, Jenner P, Marsden C D
Parkinson's Disease Society Experimental Research Laboratories, King's College, London, UK.
Psychopharmacology (Berl). 1992;109(1-2):49-56. doi: 10.1007/BF02245479.
The ability of selective D-1 agonist and antagonist drugs to alter motor deficits and locomotor activity was studied in MPTP-treated common marmosets. Both the D-2 agonist quinpirole and the mixed D-1/D-2 agonist apomorphine reversed the motor impairments and induced locomotor activity. The D-1 antagonist SCH 23390 and the D-2 antagonist raclopride given alone further reduced motor function in MPTP-treated animals. The actions of quinpirole were potently and completely inhibited by raclopride but only partially and inconsistently by SCH 23390. In contrast, the effects of apomorphine were markedly but incompletely inhibited by both raclopride and SCH 23390. The D-1 agonist SKF 38393 alone caused a dose related reduction in motor activity. SKF 38393 weakly and partially inhibited the improvements in motor function produced by quinpirole but had a more pronounced effect on apomorphine induced motor activity. The induction of motor activity in MPTP treated common marmosets may separately involve both D-1 and D-2 receptors. Comparison with our previous data on the effect of the same drugs in normal common marmosets provides some evidence for a breakdown of linkage between D-1 and D-2 systems following MPTP treatment. The actions of SKF 38393 in MPTP-treated common marmosets contrasts with its ability to induce behavioural activation and a facilitation of D-2 mediated behaviour in rodents. SKF 38393 may not be the compound with which to delineate the role of D-1 receptors in primates.
在经1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的普通狨猴中，研究了选择性D-1激动剂和拮抗剂药物改变运动缺陷和运动活动的能力。D-2激动剂喹吡罗和D-1/D-2混合激动剂阿扑吗啡均可逆转运动障碍并诱导运动活动。单独给予D-1拮抗剂SCH 23390和D-2拮抗剂雷氯必利会进一步降低MPTP处理动物的运动功能。喹吡罗的作用被雷氯必利有效且完全抑制，但仅被SCH 23390部分且不一致地抑制。相比之下，阿扑吗啡的作用被雷氯必利和SCH 23390均显著但不完全抑制。单独使用D-1激动剂SKF 38393会导致运动活动呈剂量相关的降低。SKF 38393对喹吡罗产生的运动功能改善有微弱且部分的抑制作用，但对阿扑吗啡诱导的运动活动有更明显的影响。MPTP处理的普通狨猴中运动活动的诱导可能分别涉及D-1和D-2受体。与我们之前关于相同药物对正常普通狨猴作用的数据进行比较，为MPTP处理后D-1和D-2系统之间的联系中断提供了一些证据。SKF 38393在MPTP处理的普通狨猴中的作用与其在啮齿动物中诱导行为激活和促进D-2介导行为的能力形成对比。SKF 38393可能不是用于阐明D-1受体在灵长类动物中作用的化合物。
