Ahlenius S, Ericson E, Wijkström A
Department of Behavioral Pharmacology, Astra Arcus AB, Södertälje, Sweden.
J Pharm Pharmacol. 1993 Mar;45(3):237-9. doi: 10.1111/j.2042-7158.1993.tb05543.x.
Male Sprague-Dawley rats were treated subcutaneously with reserpine (5 mg kg-1, -18 h) and with the aromatic amino acid decarboxylase inhibitor, NSD-1015 (3-hydroxybenzylhydrazine) (100 mg kg-1 -30 min). Remoxipride 0.8, 3.2 or 12.8 mg kg-1 was administered subcutaneously at -50 min. Immediately following decapitation (0 h), the ventral striatum and the anterior neocortex were dissected. Dopa and 5-hydroxytryptophan accumulation in these brain areas were analysed by HPLC with electrochemical detection. Reserpine produced a marked increase in striatal and neocortical dopa accumulation, in comparison with glucose vehicle + NSD-1015-treated controls, and this increase was dose-dependently antagonized by remoxipride treatment. Thus, together with demonstrated dopamine receptor antagonist actions in intact animals, remoxipride behaves as a mixed dopamine receptor agonist-antagonist. Such properties could contribute to the favourable endocrine and extrapyramidal side effect profile of remoxipride as an antipsychotic agent.
将雄性斯普拉格-道利大鼠皮下注射利血平（5毫克/千克，-18小时）和芳香族氨基酸脱羧酶抑制剂NSD-1015（3-羟基苄基肼）（100毫克/千克，-30分钟）。在-50分钟时皮下注射0.8、3.2或12.8毫克/千克的瑞莫必利。断头后立即（0小时），解剖腹侧纹状体和前新皮层。通过高效液相色谱-电化学检测分析这些脑区中多巴和5-羟色氨酸的积累。与葡萄糖载体+NSD-1015处理的对照组相比，利血平使纹状体和新皮层中多巴的积累显著增加，并且这种增加被瑞莫必利治疗剂量依赖性地拮抗。因此，与在完整动物中证明的多巴胺受体拮抗剂作用一起，瑞莫必利表现为混合多巴胺受体激动剂-拮抗剂。这些特性可能有助于瑞莫必利作为抗精神病药物具有良好的内分泌和锥体外系副作用谱。
