In vitro characterization of a novel, potent and selective M-3 antagonist

[摘要] The pharmacological profile of the competitive muscarinic antagonist (2S, 3'R) 3-quinuclidinyl tropate, abbreviated (-)-2a, was evaluated on rabbit vas deferens (M-1/M-4-like; pA(2)=9.10), guinea-pig left atrium (M-2; pA(2)=9.30), guinea-pig ileum (M-3; pA(2)=10.33) and guinea-pig uterus (M-4 putative; pA(2)=9.70) muscarinic receptors and on the five subtypes of muscarinic receptors expressed individually in CHO-K1 cells. The drug shows an affinity for the M-3 receptor subtype at least 10-fold higher than 4-DAMP, p-HHSiD and zamifenacin, used as reference drugs. These results suggest (-)-2a as a novel, potent and selective M-3 antagonist that may have therapeutic potential in the treatment of conditions associated with increased smooth muscle contractility.

[发布日期] 1997-08-22

[关键词] M-1 receptors;M-2 receptors;M-3 receptors;M-4 receptors;muscarinic antagonist