Abstract
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.
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