Micheletti R, Montagna E, Giachetti A
J Pharmacol Exp Ther. 1987 May;241(2):628-34.
The M2 subtype of the muscarinic receptor was investigated using the antagonist AF-DX 116. In "in vitro" and "in vivo" experiments, AF-DX 116 behaved as a competitive antagonist and exhibited a selectivity for cardiac muscarinic-mediated functions. It antagonized negative chronotropic and inotropic effects exerted by muscarinic receptor activation in the guinea pig atria with an affinity (pA2) 10-fold greater than that estimated in intestinal and tracheal smooth muscle preparations. It also reversed the negative chronotropic effect induced by peripheral vagal stimulation, intrasinus node injection of bethanechol and central vagal activation by clonidine. In all these in vivo functions, AF-DX 116 was approximately 10 times less potent than atropine, while being several hundred-fold less potent in antagonizing acetylcholine-mediated bronchoconstriction and gastric emptying. These results are consistent with the hypothesis that the cardiac muscarinic receptors constitute a subclass of the M2 subtype.
使用拮抗剂AF-DX 116对毒蕈碱受体的M2亚型进行了研究。在“体外”和“体内”实验中，AF-DX 116表现为竞争性拮抗剂，对心脏毒蕈碱介导的功能具有选择性。它拮抗了豚鼠心房中由毒蕈碱受体激活所产生的负性变时和变力作用，其亲和力（pA2）比在肠道和气管平滑肌制剂中估计的亲和力大10倍。它还逆转了外周迷走神经刺激、窦房结内注射氨甲酰甲胆碱以及可乐定引起的中枢迷走神经激活所诱导的负性变时作用。在所有这些体内功能中，AF-DX 116的效力约为阿托品的1/10，而在拮抗乙酰胆碱介导的支气管收缩和胃排空方面，其效力要低数百倍。这些结果与心脏毒蕈碱受体构成M2亚型一个亚类的假说一致。
