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Stereoselectivity at muscarinic receptor subtypes: observations with the enantiomers of phenglutarimide
Author(s) -
Lambrecht Günter,
Feifel Roland,
Mutschler Ernst
Publication year - 1989
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530010212
Subject(s) - chemistry , stereoselectivity , muscarinic acetylcholine receptor , enantiomer , pirenzepine , receptor , stereochemistry , muscarinic acetylcholine receptor m1 , muscarinic acetylcholine receptor m2 , antagonist , pharmacology , biochemistry , biology , catalysis
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.