Gnanalingham K K, Hunter A J, Jenner P, Marsden C D
Parkinson's Disease Society, Experimental Research Laboratories, King's College, London, U.K.
Psychopharmacology (Berl). 1995 Feb;117(3):287-97. doi: 10.1007/BF02246103.
The effects of co-administration of quinpirole with benzazepine D1 dopamine (DA) agonists possessing full/supramaximal (SKF 80723 and SKF 82958), partial (SKF 38393 and SKF 75670) and no efficacies (SKF 83959) in stimulating adenylate cyclase (AC) were investigated in rodent and primate models of Parkinson's disease (PD). In rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle, co-administration of SKF 38393 (7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine), SKF 75670 (3-CH3 analogue), SKF 80723 (6-Br analogue), SKF 83959 (6-Cl, 3-CH3, 3'-CH3 analogue) and SKF 82958 (6-Cl, 3-C3H5 analogue) strongly potentiated the contralateral circling induced by quinpirole. In MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) treated common marmosets, administration of quinpirole alone increased locomotor activity and reversed motor deficits. Grooming and oral activity were unaltered. Co-administration of SKF 38393 and SKF 75670 inhibited the quinpirole-induced changes in locomotor activity and motor disability. The combined treatment of SKF 80723 or SKF 82958 with quinpirole had no overall effect on locomotor activity or motor disability. In contrast, SKF 83959 extended the duration of the quinpirole-induced increase in locomotor activity with corresponding decreases in motor disability. Co-administration of high doses of SKF 82958 and more especially SKF 83959 and SKF 80723, with quinpirole induced hyperexcitability and seizures. Oral activity and grooming were unaltered following the co-administration of benzazepine derivatives with quinpirole. The ability of some benzazepine D1 DA agonists to prolong the antiparkinsonian effects of quinpirole in the MPTP-treated marmoset may indicate a role for certain D1 DA agonists in the clinical treatment of PD. In general, the behavioural responses to the combined administration of benzazepines with quinpirole in the 6-OHDA lesioned rat and more especially the MPTP-treated marmoset failed to correlate with their ability to stimulate AC. These observations further implicate a behavioural role for D1 DA receptors not linked to AC.
在帕金森病（PD）的啮齿动物和灵长类动物模型中，研究了喹吡罗与具有刺激腺苷酸环化酶（AC）的完全/超最大效应（SKF 80723和SKF 82958）、部分效应（SKF 38393和SKF 75670）和无效应（SKF 83959）的苯并氮杂卓D1多巴胺（DA）激动剂联合给药的效果。在单侧内侧前脑束6-羟基多巴胺（6-OHDA）损伤的大鼠中，联合给予SKF 38393（7,8-二羟基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓）、SKF 75670（3-甲基类似物）、SKF 80723（6-溴类似物）、SKF 83959（6-氯、3-甲基、3'-甲基类似物）和SKF 82958（6-氯、3-丙基类似物）可强烈增强喹吡罗诱导的对侧旋转。在1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的普通狨猴中，单独给予喹吡罗可增加运动活性并逆转运动缺陷。梳理和口腔活动未改变。联合给予SKF 38393和SKF
