盐酸苯环壬酯左旋体及光学异构体抗动物晕动病药效学研究  

Comparative study on anti-motion sickness efficacy of R-phencynonate hydrochloride and its optical isomers

作　　者：李更[1] 王丽韫[1] 郑建全[1] 刘河[1] 仲伯华[1] 刘克良[1] 

机构地区：[1]军事医学科学院毒物药物研究所

出　　处：《中华航空航天医学杂志》2006年第2期87-91,共5页Chinese Journal of Aerospace Medicine

基　　金：国家自然科学基金重大项目(203900508)

摘　　要：目的评价盐酸苯环壬酯左旋体[R(-)-PCH]对晕动病的防治作用。方法建立两个实验动物模型:①家兔右侧颈总动脉局部帖敷强胆碱酯酶抑制剂对氧磷10μl(380μg/10μl),家兔出现逆向(左侧)转圈,逆向转圈3圈/min以上为晕动病阳性症状,实验前20 min灌胃给药,观察盐酸苯环壬酯及其光学异构体对家兔晕动病的防治作用;②家猫右侧大腿深部肌肉注射毒扁豆碱(0.6 mg/kg),引起家猫腹部不适、恶心、呕吐等晕动病(MS)样综合征,实验前20 min灌胃给药。观察盐酸苯环壬酯消旋体及其光学异构体对家猫晕动病样综合征的预防和治疗作用。结果兔逆向转圈综合症模型中盐酸苯环壬酯左旋体的半数有效剂量(ED50)为4.01 mg/kg,外消旋体的ED50为8.94 mg/kg,两者的ED50比为1∶2.23(P<0.05),而盐酸苯环壬酯的右旋体[S(+)-PCH]在34 mg/kg没有表现出明显的抗晕动病效果(P>0.05);在家猫晕动病样综合症模型中,R(-)-PCH的ED50值为0.07 mg/kg,外消旋体的ED50值为0.58 mg/kg,两者的ED50值比为1∶8.29(P<0.01),而S(+)-PCH在3.0 mg/kg没有表现出明显的抗晕动病效果(P>0.05)。结论盐酸苯环壬酯的左旋体抗晕动病效果明显强于外消旋体和右旋体,将来可能会成为抗晕动病的新药。Objective To evaluate potency of R-phencynonate hydrochloride [R（-）-PCH] and compare with its optical isomers in prevention and treatment of motion sickness（MS）. Methods Two kinds of MS animal model were established.① Rabbit model： 380 μg paraoxon （a kind of strong cholinesterase inhibitor） was applied locally around the right carotid artery under local anesthesia to induce MS. The criteria of MS positive was that the forced reverse circling of the animal exceeded 3 per minute. Twenty minutes before experiment, saline, R（ -）-PCH, PCH or S（-t-）-PCH 1.0 ml/kg was given by gastric infusion respectively in control group and 3 experimental group. The MS symptom was observed after application of paraoxon for 2 h.②Cats model： Esterine （0. 60 mg/kg） was given intramuscularly to induce MS symptom, three kind of anti MS drugs were given 20 rain before experiment to determine their anti MS efficacy. Results In rabbit model, the median effective dose（ED50） of R（- ）-PCH and PCH for inhibiting adverse circling were 4.01 mg/kg and 8.94 mg/kg, respectively, ED50 ratio between these two was 1 ： 2.23 （P〈0.05）; in the cat model, the ED50 were 0.07 mg/kg and 0. 58 mg/kg respectively, ED50 between R（-）-PCH and PCH was 1 ： 8.29 （P〈 0.01）. S（＋）-PCH at the given dose （34 mg/kg） did not show significant anti-MS effect in both animal models. Condusions The anti-MS efficacy of R（- ）-PCH is higher than its racemate and S（＋）- PCH. R（-）-PCH maybe developed as an anti-MS drug in the future.

关 键 词：盐酸苯环壬酯 晕动病 受体 胆碱能 手性药物 

分 类 号：R96[医药卫生—药理学]