左旋千金藤立定和12-氯斯阔任旋光异构体对黑质多巴胺神经元放电活动的比较(英文)  

( - )-Stepholidine vs 12-chloroscoulerine enantiomers on firing activity of substantia nigral dopamine neurons

作　　者：张雪翔[1] 金国章 

机构地区：[1]中国科学院上海药物研究所

出　　处：《中国药理学报》1996年第1期18-22,共5页Acta Pharmacologica Sinica

基　　金：Project supported by the National Natural Science Foundation of China,№ 39320001,39130091.

摘　　要：目的:比较左旋千金藤立定((-)-stepholidine,(-)-SPD)和12-氯斯阔任(12-chloroscoulerine,CSL)对黑质(substantia nigra,SN)多巴胺(DA)神经元放电的影响。方法:麻痹大鼠上的胞外单单位记录。结果:在大鼠,(-)-SPD,(-)-,(±)-和(+)-CSL减弱iv 10μg·kg^(-1)阿朴吗啡引起的放电抑制。ED_(50)值分别为15.1(11.9—19.4),7.8(7.0—8.7),12.6(2.0—17.9)μg·kg^(-1)和2.9(2.6—3.3)mg·kg^(-1)。(-)-CSL比(-)-SPD强1倍,比(+)-CSL强371倍。在利血平化大鼠,(-)-SPD,(-)-,(±)-,和(+)-CSL减弱4mg·kg^(-1)SKF-38393引起的放电抑制。ED_(50)值为0.53(0.51—0.55),0.51(0.43—0.60),1.2(0.7—2.0)和5.9(4.9—7.1)mg·kg^(-1)。(-)-CSL的强度与(-)-SPD相似,比(+)-CSL强11倍。结论:(-)-SPD和CSL是D_1/D_2混合性阻滞剂。(-)-CSL最强,(+)-CSL最弱。AIM: To compare the potencies between ( - )-stepholidine ((-)SPD) and 12-chloroscoulerine (CSL) enantiomers on firing of substantia nigra (SN) dopamine (DA.) neurons. METHODS: Extracellular single unit recordings in paralyzed rats. RESULTS: In rats, (-)-SPD, ( -)-, (±)-, and ( + )-CSL attenuated iv apomorphine (Apo, 10 μg·kg -1)-induced inhibition on firing of DA cell, and their ED50 values were 15.1 (11.9-19.4), 7.8 (7.0-8.7), 12.6 (2.0 -17.9) ?g·kg-1, and 2.9 (2.6-3.3) mg·kg-1, respectively. Thus, (- )-CSL was 1 time more potent than ( - )-SPD and 371 times more potent than ( + )-CSL on D2 receptors. In reserpinized rats, (-)-SPD, (-)-, (±)-, and ( + )-CSL blocked the inhibition caused by iv 4 mg · kg-1 SKF-38393, with ED50 values of 0.53 (0.51 -0.55), 0.51 (0.43-0.60), 1.2 (0.7-2.0), and 5. 9 (4. 9-7. 1) mg·kg-1, respectively. The potency of (-)-CSL was similar to that of (- )-SPD on D1 receptors and 11 times higher than that of ( + )-CSL. CONCLUSION: CSL enantiomers are D1/D2 mixed antagonists as (-)-SPD. ( - )-CSL is the most, while ( + )-CSL is the least, potent one among them.

关 键 词：千金藤立定 12-氯斯阔任 电生理学 多巴胺 

分 类 号：R964[医药卫生—药理学]