Micheletti R, Schiavone A
Department of Pharmacology, Istituto De Angeli, Milano, Italy.
J Pharmacol Exp Ther. 1990 Apr;253(1):310-4.
The affinity (KA) of 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343), acting as an agonist of M1 muscarinic receptors, has been estimated by means of fractional receptor inactivation, employing the irreversible muscarinic antagonist propylbenzylcholine mustard. Two M1-mediated responses elicited by McN-A-343 were studied: relaxation of the isolated rat duodenum and inhibition of twitch contractions in rabbit was deferens. A comparison was made with the affinity of McN-A-343 as an antagonist (KB) of acetylcholine-induced contraction in rat duodenum. Results showed that McN-A-343 displayed similar affinities as an agonist and as an antagonist: -log KA were 4.68 and 5.17 in duodenum and vas deferens, respectively, vs. -log KB of 4.96 in duodenum, indicating that the ability of McN-A-343 to selectively stimulate M1 receptors is not based on a greater affinity for this subtype. In both preparations examined, McN-A-343 reached maximum effect through occupation of a fraction of the total available receptors (approximately 30% in duodenum, approximately 80% in vas deferens), implying that occupation of M1 receptors is translated into effect in a highly efficient way.
4-（间氯苯基-氨甲酰氧基）-2-丁炔基三甲基氯化铵（McN-A-343）作为M1毒蕈碱受体激动剂的亲和力（KA），已通过使用不可逆的毒蕈碱拮抗剂丙基苄基胆碱芥子气，采用部分受体失活的方法进行了估算。研究了McN-A-343引发的两种M1介导的反应：离体大鼠十二指肠的舒张和兔输精管抽搐收缩的抑制。并将McN-A-343作为大鼠十二指肠中乙酰胆碱诱导收缩的拮抗剂（KB）的亲和力进行了比较。结果表明，McN-A-343作为激动剂和拮抗剂表现出相似的亲和力：在十二指肠和输精管中，-log KA分别为4.68和5.17，而在十二指肠中-log KB为4.96，这表明McN-A-343选择性刺激M1受体的能力并非基于对该亚型更高的亲和力。在所检查的两种制剂中，McN-A-343通过占据一部分总可用受体（十二指肠中约30%，输精管中约80%）达到最大效应，这意味着M1受体的占据以高效的方式转化为效应。
