In vitro characterization of a novel, potent and selective M3 antagonist

The pharmacological profile of the competitive muscarinic antagonist (2S, 3'R) 3-quinuclidinyl tropate, abbreviated (-)-2a, was evaluated on rabbit vas deferens (M1/M4-like; pA2=9.10), guinea-pig left atrium (M2; pA2=9.30), guinea-pig ileum (M3; pA2=10.33) and guinea-pig uterus (M4 putative; pA2=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 M3 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 M3 antagonist that may have therapeutic potential in the treatment of conditions associated with increased smooth muscle contractility