title: Stereoselective interaction of procyclidine, hexahydro-difenidol, hexbutinol and oxyphencyclimine, and of related antagonists, with four muscarinic receptors.
abstract: We investigated the binding properties of the (R)- and (S)-enantiomers of the muscarinic antagonists trihexyphenidyl, procyclidine, hexahydro-difenidol, p-fluoro-hexahydro-difenidol, hexbutinol, p-fluoro-hexbutinol, and their corresponding methiodides at muscarinic M1, M2, M3 and M4 receptor subtypes. In addition, binding properties of the (R)- and (S)-enantiomers of oxyphencyclimine were studied. The (R)- enantiomers (eutomers) of all the compounds had a greater affinity than the (S)-isomers for the four muscarinic receptor subtypes. The binding patterns of the (R)- and (S)-enantiomers were generally different. We did not observe any general correlation between the potency of the high-affinity enantiomer and the affinity ratio (eudismic ratio) of the two enantiomers. The results are discussed in terms of a 'four subsites' binding model.
authors.affiliation: Department of Biochemistry and Nutrition, Medical School, Free University of Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Waelbroeck
authors.forename: J
authors.initials: J
authors.lastname: Camus
authors.forename: M
authors.initials: M
authors.lastname: Tastenoy
authors.forename: E
authors.initials: E
authors.lastname: Mutschler
authors.forename: C
authors.initials: C
authors.lastname: Strohmann
authors.forename: R
authors.initials: R
authors.lastname: Tacke
authors.forename: L
authors.initials: L
authors.lastname: Schjelderup
authors.forename: A
authors.initials: A
authors.lastname: Aasen
authors.forename: G
authors.initials: G
authors.lastname: Lambrecht
authors.forename: J
authors.initials: J
authors.lastname: Christophe
mesh_terms: D000480:Alkynes / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D019832:N-Methylscopolamine; D009447:Neuroblastoma; D010179:Pancreas / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011352:Procyclidine / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012602:Scopolamine Derivatives / Q000494:pharmacology; D013237:Stereoisomerism; D014316:Tritium
chemical_list: D000480:Alkynes; D010276:Parasympatholytics; D010880:Piperidines; D011743:Pyrimidines; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D014316:Tritium; C060685:hexahydrodifenidol; C063963:hexbutinol; C100201:oxyphencyclimine; D011352:Procyclidine; D019832:N-Methylscopolamine