Stereoselectivity at muscarinic receptor subtypes: observations with the enantiomers of phenglutarimide

The affinity of the enantiomers of phenglutarimide at three muscarinic receptor subtypes was examined in vitro using field‐stimulated rabbit vas deferens (M 1 receptors) and guinea pig atria (M 2α receptors) and ileum (M 2β receptors). Extremely high stereoselectivity was observed and higher affinities (up to 6000‐fold) were found for the (+)‐S‐enantiomer. The stereoselectivity ratios were different at the three subtypes, and the stereochemical demands made by the muscarinic receptors were most stringent at M 1 receptors. (+)‐(S)‐Phenglutarimide was found to be a potent M 1 ‐selective antagonist (p A 2 at M 1 = 8.53). Its receptor selectivity profile is qualitatively similar to that of pirenzepine. (−)‐(R)‐Phenglutarimide showed no comparable discriminatory properties.