Saunders J, Freedman S B
Trends Pharmacol Sci. 1989 Dec;Suppl:70-5.
In the present study we describe a novel series of oxadiazole based tertiary amines which include the most efficacious and potent muscarinic ligands known. These compounds possess physicochemical characteristics which enable rapid equilibration into the CNS and are able to fully activate cortical muscarinic receptors. Data obtained from this series have allowed us to propose a pharmacophoric model which distinguishes high and low affinity state binding. This in turn has led us to suggest that agonists and antagonists may bind at two independent sites on the receptor protein and to speculate on the steps putatively involved in agonist-induced receptor activation.
在本研究中，我们描述了一系列新型的基于恶二唑的叔胺，其中包括已知最有效和最具活性的毒蕈碱配体。这些化合物具有能够快速进入中枢神经系统的物理化学特性，并能够完全激活皮层毒蕈碱受体。从该系列获得的数据使我们能够提出一个区分高亲和力和低亲和力状态结合的药效团模型。这反过来又使我们提出激动剂和拮抗剂可能在受体蛋白的两个独立位点结合，并推测激动剂诱导受体激活可能涉及的步骤。
