氯代斯阔任旋光异构体作用于多巴胺受体对动物行为的比较(英文)

Comparison of 12-chloroscoulerine enantiomers on animal behavior to dopamine receptors

目的:比较氯代斯阔任(CSL)旋光异构体对DA受体的作用特性。方法:采用小牛纹状体DA受体结合分析和小鼠、大鼠的行为实验。结果:d-CSL对D_1和D_2受体的K_i值分别是135和9150nmol·L^(-1),而l-CSL对D_1和D_2的亲和力(K_i)均为5.7nmol·L^(-1),分别为d-CSL的24倍和1605倍。dl-CSL对D_1和D_2受体的K_i值分别为8.9和9.6nmol·L^(-1),比l-CSL稍弱。大鼠刻板活动和木僵实验、小鼠的跳跃和自发活动实验均证明CSL旋光异构体对DA受体有阻滞作用。结论:CSL旋光异构体为DA受体阻滞剂的作用特性,其作用强度为:l-CSL>dl-CSL>>d-CSL。

AIM; To compare the pharmacological characteristics of 12-chloroscoulerine (CSL) enantiomers to dopamine (DA) receptors. METHODS: Radioligand receptor binding assay with calf striatum and behavioral tests of mice or rats were used. RESULTS: In the competitive binding assay, the affinities (Ki) of l-CSL to D1 and D2 receptors were 5.7 nmol·L-1, while those of d-CSL for D1 and D2 receptors were 135 and 9150 nmol ·L-1, respectively. The Ki of dl-CSL to D1 and D2 recptors were 8.9 and 9.6 nmol · L -1, respectively, which were slightly weaker than that of l-CSL. In the behavioral experiments, CSL enantiomers 5 - 60 mg· kg-1 antagonized the stereotypy induced by apomorphine in rats, and 5 - 150 mg · kg-1 produced catalepsy. The enantiomers 10-60 mg·kg-1 reduced the mice jumping behavior induced by amphetamine + levodopa. l-CSL 10-80 mg · kg-1 antagonized the spontaneous locomotor activity of normal or amphetamine-treated mice. CONCLUSION: CSL enantiomers are antagonists to DA receptors: l-CSL > dl-CSL> > d-CSL.