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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 new targeted tropane compounds on M receptor kinetics in guinea pig ileum. Methods The cumulative dose-response curve of the longitudinal muscle of ileum isolated from guinea pigs was used to determine the pD2 (negative logarithm of dissociation constant) and Emax (maximum effect) values. ACh was used as a standard to compare the affinity and intrinsic activity. The MAC-6, MAC-7, MAC-8, MAC-18 and MAC-19 compounds had varying degrees of affinity with the guinea pig intestinal longitudinal muscle M receptor (pD2 = 6.59-8.77) The maximal effect of contraction was 29% ~ 57% of ACh. Atropine, a selective antagonist of M receptor, could block its action. On the contrary, MAC-16 could significantly inhibit contraction of longitudinal muscle of ACR-induced gonads, pA2 was 7.72 .Conclusion Oriented syndiotactic compounds have significant M receptor agonistic or blocking effects and show obvious structure-activity relationship.