title: Competitive and allosteric binding of 2 alpha-DHET and its optical isomers to rat cardiac muscarinic receptors.
abstract: The possibility of both competitive and allosteric interactions of 2 alpha-(2',2'-disubstituted-hydroxy-ethoxy)tropane (2 alpha-DHET) and its four optical isomers with rat cardiac muscarinic receptors was studied. 2 alpha-DHET and its optical isomers competitively inhibited the binding of [3H] quinuclidinyl benzilate to rat cardiac muscarinic receptors and allosterically decelerated the dissociation of bound [3H] quinuclidinyl benzilate in a concentration-dependent manner. The rank order of potencies to displace [3H] quinuclidinyl benzilate binding was 1R-2 alpha-2'R > 1S-2 alpha-2'R > 2 alpha-DHET > 1S-2 alpha-2'S > 1R-2 alpha-2'S, while their potencies to decelerate the dissociation of bound [3H] quinuclidinyl benzilate were not significantly different. The allosteric potencies were found not to be correlated with their binding potencies.
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Z G
authors.initials: ZG
authors.lastname: Gao
authors.forename: C G
authors.initials: CG
authors.lastname: Liu
mesh_terms: D000495:Allosteric Site; D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects*; D008297:Male; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013997:Time Factors; D014326:Tropanes / Q000494:pharmacology*
chemical_list: D011976:Receptors, Muscarinic; D014326:Tropanes; C094207:2-(2'-cyclopentyl-2'-phenyl-2'-hydroxyethoxy)tropane; D011813:Quinuclidinyl Benzilate