Stereoselectivity of the enantiomers of trihexyphenidyl and its methiodide at muscarinic receptor subtypes.
High stereoselectivity was observed for the enantiomers of trihexyphenidyl and trihexyphenidyl methiodide at muscarinic M1-receptors in field-stimulated rabbit vas deferens and at M2 alpha- and M2 beta-receptors in guinea-pig atrium and ileum, respectively. Considerably higher affinities (up to 1700-fold) were found for the (R)-(-)-enantiomers. The stereochemical demands made by the muscarinic receptor subtypes were most stringent at the M1-receptors. The (R)-(-)-enantiomers were found to be potent M1-selective antagonists (pA2 = 10.1/10.6). They showed a 91- and 45-fold selectivity for M1- over M2 alpha-receptors, respectively.
Lambrecht
G
G
Department of Pharmacology, University of Frankfurt, Federal Republic of Germany.
Feifel
R
R
Moser
U
U
Aasen
A J
AJ
Waelbroeck
M
M
Christophe
J
J
Mutschler
E
E
D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D014282:Trihexyphenidyl / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D011976:Receptors, Muscarinic; D014282:Trihexyphenidyl