新型茛菪烷类化合物对豚鼠回肠肌M受体动力学研究

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。

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

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.