Ogren S O, Hall H, Köhler C, Magnusson O, Sjöstrand S E
Psychopharmacology (Berl). 1986;90(3):287-94. doi: 10.1007/BF00179179.
The actions on central dopamine (DA) mechanisms of raclopride, a new substituted benzamide, were studied by means of behavioural and biochemical methods in the rat. Raclopride blocked the in vitro binding of the dopamine D2 antagonist 3H-spiperone (IC50 = 32 nM), but not of the unselective D1 antagonist 3H-flupenthixol (IC50 greater than 100,000 nM) in rat striatum, and failed to inhibit striatal DA-sensitive adenylate cyclase in vitro (IC50 greater than 100,000 nM). Raclopride caused a dose-dependent increase in the DA metabolites HVA and DOPAC in the striatum and olfactory tubercle. Behavioural studies showed that raclopride discriminates between the motor behaviours induced by the DA agonist apomorphine. Thus, unlike haloperidol, raclopride blocked apomorphine-induced hyperactivity at considerably lower doses than those inhibiting oral stereotypies. Moreover, raclopride showed a high separation between the doses for blockade of apomorphine-induced hyperactivity and those inducing catalepsy in rats. Raclopride caused a dose-dependent blockade of the specific binding of 3H-spiperone and 3H-N-n-propylnorapomorphine (3H-NPA) in vivo at doses similar to those blocking the behavioural effects of apomorphine. The maximal blockade of 3H-spiperone binding in vivo was lower for raclopride than for haloperidol. Raclopride caused a greater inhibition of 3H-NPA than of 3H-spiperone in vivo binding in the striatum. It is suggested that the ability of raclopride to discriminate between different DA-mediated functions may be attributed to a preferential blockade of a subclass of functionally coupled dopamine D2 receptors in striatal as well as in extrastriatal brain regions in the rat.
采用行为学和生物化学方法，在大鼠中研究了新型取代苯甲酰胺雷氯必利对中枢多巴胺（DA）机制的作用。雷氯必利可阻断多巴胺D2拮抗剂3H-螺哌隆在体外与大鼠纹状体的结合（IC50 = 32 nM），但不影响非选择性D1拮抗剂3H-氟哌噻吨的结合（IC50大于100,000 nM），且在体外不能抑制纹状体中DA敏感的腺苷酸环化酶（IC50大于100,000 nM）。雷氯必利可使纹状体和嗅结节中DA代谢产物高香草酸（HVA）和3,4-二羟基苯乙酸（DOPAC）呈剂量依赖性增加。行为学研究表明，雷氯必利能区分DA激动剂阿扑吗啡诱导的运动行为。因此，与氟哌啶醇不同，雷氯必利阻断阿扑吗啡诱导的多动所需剂量远低于抑制口腔刻板行为的剂量。此外，雷氯必利在阻断阿扑吗啡诱导的多动和诱导大鼠僵住症的剂量之间有很大差异。雷氯必利在体内以与阻断阿扑吗啡行为效应相似的剂量，引起3H-螺哌隆和3H-N-正丙基去甲阿扑吗啡（3H-NPA）特异性结合的剂量依赖性阻断。雷氯必利在体内对3H-螺哌隆结合的最大阻断作用低于氟哌啶醇。雷氯必利在体内对纹状体中3H-NPA结合的抑制作用大于对3H-螺哌隆结合的抑制作用。提示雷氯必利区分不同DA介导功能的能力，可能归因于其对大鼠纹状体及纹状体以外脑区中功能偶联的多巴胺D2受体亚类的优先阻断。
