新型莨菪烷类化合物对豚鼠回肠肌M受体动力学研究  

Effects of Newly Synthesized Nortropane Derivatives on Muscarinic-receptors in Guinea Pig Ileum

作　　者：崔永耀[1] 冯菊妹[1] 刘慧中[2] 孙玉燕[1] 荣征星[1] 陆阳[2] 陈红专[1] 

机构地区：[1]上海第二医科大学药理学教研室,上海200025 [2]上海第二医科大学化学教研室,上海200025

出　　处：《上海第二医科大学学报》2000年第1期22-24,共3页Acta Universitatis Medicinalis Secondae Shanghai

基　　金：上海市高等学校科学技术发展基金!98B5;上海市科技发展基金!9970204

摘　　要：目的探讨定向合成新型莨菪烷类化合物对豚鼠回肠肌Ｍ受体动力学的作用。方法采用豚鼠离体回肠纵肌累积剂量－效应曲线法，求得ｐＤ２（解离常数负对数）及Ｅｍａｘ（最大效应）值，以乙酰胆碱（ＡＣｈ为标准品，比较其亲和力和内在活性。结果ＭＡＣ－６、ＭＡＣ－７、ＭＡＣ－８、ＭＡＣ－１８和ＭＡＣ－１９化合物与豚鼠肠纵肌Ｍ受体具有不同程度的亲和力（ｐＤ２＝６．５９～８．７７），引起豚鼠肠纵肌收缩最大效应为ＡＣｈ的２９％～５７％，选择性Ｍ受体拮抗药阿托品能阻断其作用；相反，ＭＡＣ－１６能显著抑制由ＡＣｈ引起豚鼠肠纵肌收缩，呈竞争性拮抗作用，其ｐＡ２为７．７２。结论定向合成莨菪烷类化合物具有明显的Ｍ受体激动或阻断作用，并显示明显的构效关系特征。Objective To investigate the effects of newly synthesized 12 nortropane derivatives (MAC), related in structure to Baogongtang A, on muscarinic-recep tors in the guinea pig ileum. Methods Isolated lieal longitudinal lieal muscles of the guinea pigs were used to evaluate the antagonistic parameter (pD2) and efficacy (Emax) for muscarinic-receptors by the eumulative concentration-contraction curve method. Results The data showed that several compounds such as MAC-6, MAC-7, MAC-8, MAC-18 and MAC-19 could elicit potent contractions of the lieal muscles with pD2(6.59-8.77), and at the highest tested concentration produce 29%-57% maximum contraction fiom acetylcholine (ACh). This agonistic effect was blocked by atropine, a selesctive muscarinic-receptor antagonist. In contrast, MAC16 could antagonize ACh-indu ced contractions of the lieal muscles and behaved as competitive muscarinic antagonists with pA2 of 7.72. Conclusion The above nortropane derivatives possessed significant muscarinic-receptor agonistic or antagonistic activities with apparent structure-activity relationship.

关 键 词：莨菪烷类化合物 回肠肌 M受体 乙酰胆碱 

分 类 号：R966[医药卫生—药理学]