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 (M1 receptors) and guinea pig atria (M2 alpha receptors) and ileum (M2 beta 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.
Lambrecht
G
G
Department of Pharmacology, University of Frankfurt, Federal Republic of Germany.
Feifel
R
R
Mutschler
E
E
D000818:Animals; D004558:Electric Stimulation; D005260:Female; D005984:Glutethimide / Q000031:analogs & derivatives* / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010276:Parasympatholytics / Q000378:metabolism; D010890:Pirenzepine / Q000494:pharmacology; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013237:Stereoisomerism; D014649:Vas Deferens / Q000378:metabolism
D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D010890:Pirenzepine; C005440:phenglutarimide; D005984:Glutethimide