中国药理学与毒理学杂志2011，Vol.25Issue(4)：333-338,6.DOI:10.3867/j.issn.1000-3002.2011.04.001
左旋盐酸去甲基苯环壬酯对大鼠和小鼠震颤与行为的影响
Effect of l-demethyl phencynonate hydrochloride on tremor and behavior of rats and mice
摘要
Abstract
OBJCETIVE To evaluate the therapeutic effect of anticholinergic agents l-demethyl phencynonate hydrochloride (R-DM8021) and trihexyphenidyl on Parkinson's disease (PD) modelanimals. METHODS ① The cerebral unilateral stereotactic directionally injection of6-hydroxydopamine (6-OHDA) was given to substantia nigra-striatum neurons of rats. The rotationtest evoked by apomorphine (APO) and locomotor activity were observed in the rat model after single and chronic treatment(21 d) with R-DM8021 0.2 - 2.0 mg· kg-1 and trihexyphenidyl. ②R-DM8021 0.25 -40 mg· kg-1 was ig given to mice and arecoline hydrobromide 35 mg· kg-1 was ip given 30 min later before the duration of tremor was recorded. ③ C57BL16 mice PD model was established after mice were ip given 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine ( MPTP )consecutively for 7 d and locomotor activity was observed after administration of R-DM8021 5 -20 mg·kg-1. RESULTS ① Compared with the model control group, single administration of R-DM8021 0.2, 0.5 and 2.0 mg· kg-1 increased rotation times evoked by APO by ( 17.3 ±4.5 ) ％, (29.7 ± 9.3 ) ％, (30.2 ± 13.7) ％ and (31.7 ± 5.5) ％, and for trihexyphenidyl 3.0,5.0 and 10.0 mg·kg-1 by (18.8 ±4.8)％, (22.1 ± 17.3)％ and (36.9 ±9.9)％ by trihexyphenidyl 3.0, 5.0 and 10.0 mg·kg-1. The rotation times kept increasing during R-DM8021 treatment for 21 d. ② Mice exhibited apparent tremor after arecoline hydrobromide administration. The duration was decreased significantly in R-DM8021 and trihexyphenidyl groups. ED50 of inhibition on duration time of R-DM8021 and trihexyphenidyl was (6.87 ± 1.33) mg·kg-1 and (41.14 ±9.31 )mg·kg-1, respectively. ③ Compared with normal control group, locomotor activity in MPTP model group significantly decreased. After treatment with R-DM8021 5.0, 10.0 and 20.0 and trihexyphenidyl 20.0 mg · kg-1 for 3 d, the locomotor activity of mice showed obvious improvement.CONCLUSION R-DM8021 shows better therapeutic effect on 3 PD models than trihexyphenidyl.关键词
盐酸去甲苯环壬酯/抗胆碱药/苯海索/帕金森病Key words
demethyl phencynonate hydrochloride/ anticholinergic agents/ trihexyphenidyl/Parkinson's disease分类
医药卫生引用本文复制引用
闫加庆,李昕,王丽韫,闫海涛,何新华,仲伯华,郑建全..左旋盐酸去甲基苯环壬酯对大鼠和小鼠震颤与行为的影响[J].中国药理学与毒理学杂志,2011,25(4):333-338,6.基金项目
国家"重大新药创制"科技重大专项(2009ZX09102-007) （2009ZX09102-007）
