Prinssen E P, Ellenbroek B A, Stamatovic B, Cools A R
Psychoneuropharmacological Research Unit, Catholic University of Nijmegen, Netherlands.
Eur J Pharmacol. 1993 Feb 9;231(2):275-80. doi: 10.1016/0014-2999(93)90460-y.
We investigated the role of dopamine D1 and D2 receptors in the paw test, an animal model used to assess both the antipsychotic potential and extrapyramidal side effects of drugs. The dopamine D1 receptor antagonist, SCH 39166, as well as the dopamine D2 receptor antagonist raclopride, increased the hindlimb retraction time (HRT), viz. a parameter that models antipsychotic potential, at doses that were lower than those that increased the forelimb retraction time (FRT), viz. a parameter that models extrapyramidal side effects. In contrast, the same dose of haloperidol enhanced both parameters. SCH 39166 enhanced the haloperidol- and raclopride-induced effects on FRT, whereas neither haloperidol nor raclopride enhanced the SCH 39166-induced effects upon this parameter. Except at very high doses, SCH 39166 did not alter the haloperidol- and raclopride-induced effects on HRT, and vice versa. No difference between haloperidol and raclopride was found in the interaction experiments. The clinical impact of these findings is discussed.
我们研究了多巴胺D1和D2受体在爪部试验中的作用，爪部试验是一种用于评估药物抗精神病潜力和锥体外系副作用的动物模型。多巴胺D1受体拮抗剂SCH 39166以及多巴胺D2受体拮抗剂雷氯必利，在低于增加前肢回缩时间（FRT，一种模拟锥体外系副作用的参数）的剂量下，增加了后肢回缩时间（HRT，一种模拟抗精神病潜力的参数）。相比之下，相同剂量的氟哌啶醇增加了这两个参数。SCH 39166增强了氟哌啶醇和雷氯必利对FRT的诱导作用，而氟哌啶醇和雷氯必利均未增强SCH 39166对该参数的诱导作用。除了在非常高的剂量下，SCH 39166不会改变氟哌啶醇和雷氯必利对HRT的诱导作用，反之亦然。在相互作用实验中未发现氟哌啶醇和雷氯必利之间存在差异。讨论了这些发现的临床意义。
