盐酸苯环壬酯及其衍生物抗胆碱作用比较研究  

Comparative studies of the pharmacological profiles between phencynonate hydrochloride and its derivatives

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

机构地区：[1]军事医学科学院药理毒理研究所,北京100850

出　　处：《中国药科大学学报》2006年第1期59-62,共4页Journal of China Pharmaceutical University

基　　金：国家自然科学基金重大项目资助项目(No.203900508)~~

摘　　要：目的:比较新型抗胆碱化合物盐酸苯环壬酯(CPG)及其衍生物去甲基苯环壬酯(DMCPG)、噻环壬酯(CTG)的抗胆碱作用特点。方法:运用放射性配体受体结合实验,比较研究CPG、DMCPG、CTG与大鼠大脑皮层M受体的亲和性。抗胆碱药效学作用特点用3个实验进行评价:(1)抑制氨甲酰胆碱(carbachol)对豚鼠离体回肠平滑肌的收缩作用;(2)对小鼠阈下剂量戊巴比妥镇静催眠的协同作用;(3)抑制氧化震颤素致小鼠唾液分泌作用。结果:CPG(Ki=271.37±72.30 nmol/L),CTG(Ki=540.52±124.43 nmol/L)和DMCPG(Ki=1310±263 nmol/L)均能抑制[3H]QNB与M受体的结合。中枢抗戊巴比妥镇静催眠作用从强至弱大小顺序依次为:CTG,CPG,DMCPG;抑制氧化震颤素致腺体分泌能力大小依次为:DMCPG,CPG,CTG;抑制氨甲酰胆碱对豚鼠离体回肠平滑肌收缩的作用强度大小依次为:DMCPG,CPG,CTG。结论:CPG及其衍生物CTG和DMCPG均具有较强的抗胆碱作用,但在不同组织、器官存在着药效学差异。Aim： To search for effective and selective antagonists of the muscarinic receptors, we investigated the pharmacological characteristics of novel anti-muscarinic acetylcholine agent phencynonate hydrochloride（CPG） and its derivatives suchas demethyl phencynonate hydrochloride（DMCPG） and thiencynonate hydrochloride（CTG）. Methods： Affinity of these reagents with muscarinic acetylcholine receptors from rat cerebral cortex and relative efficacies were tested by radioligand binding assay. The anticholinergic potency was assessed in three separate studies： （ 1 ） potentiating the effect of subthreshold hypnotic dose of pentobarbital, （2） inhibiting oxotremorine induced salivation and （3） inhibiting the contractile response to carbachol. Results： The Ki value of the three compounds to inhibit the binding of [^3H]NMS were （271.37 ± 72.30）nmol/L（CPG）, （540.52 ± 124.43）nmol/L（CTG） and （1310 ± 263）nmol/L （DMCPG） respectively. The central inhibitory effects were ranked in the order of CTG, CPG and DMCPG. But inhibiting carbachol-induced contraction and oxotremorine-induced salivation were DMCPC,, CPG and CTG. Conclusion： CPG and its derivatives DMCPG, CTG showed more potent anti-muscarinic characteristics and had different efficiencies in a variety of tissues and organs.

关 键 词：盐酸苯环壬酯 衍生物 M受体 抗胆碱效能 放射配体结合 

分 类 号：R96[医药卫生—药理学]