Stereoselectivity at muscarinic receptor subtypes: observations with the enantiomers of phenglutarimide
- 31 December 1988
- Vol. 1 (2) , 170-173
- https://doi.org/10.1002/chir.530010212
Abstract
The affinity of the enantiomers of phenglutarimide at three muscarinic receptor subtypes was examined in vitro using field‐stimulated rabbit vas deferens (M1 receptors) and guinea pig atria (M2α receptors) and ileum (M2β 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 M1 receptors. (+)‐(S)‐Phenglutarimide was found to be a potent M1‐selective antagonist (pA2 at M1 = 8.53). Its receptor selectivity profile is qualitatively similar to that of pirenzepine. (−)‐(R)‐Phenglutarimide showed no comparable discriminatory properties.Keywords
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