title: Allosteric and competitive interactions of 2 alpha-(2',2'-disubstituted- hydroxy-ethoxy)tropane and its optical isomers at rat central muscarinic acetylcholine receptors.
abstract: Both allosteric and competitive interactions of 2 alpha-(2',2'-disubstituted-hydroxy-ethoxy)tropane (2 alpha-DHET) and its four optical isomers with muscarinic acetylcholine receptors in rat cerebral cortex were investigated. 2 alpha-DHET and its optical isomers allosterically decelerated the dissociation of bound [3H]N-methylscopolamine in a concentration-dependent manner, but these compounds failed to decelerate the dissociation of bound [3H]quinuclidinyl benzilate. The potencies of 2 alpha-DHET and its optical isomers to decelerate the dissociation of bound [3H]N-methylscopolamine were not differed significantly, but the competitive binding potencies of these compounds were significantly different. The order of potencies of 2 alpha-DHET and its four optical isomers to inhibit the binding of [3H]quinuclidinyl benzilate to central muscarinic acetylcholine receptors was 1S-2 alpha-2'R > 1R-2 alpha-2'R > 2 alpha-DHET > 1S-2 alpha-2'S > 1R-2 alpha-2'S the isomer with 1S-2 alpha-2'R configuration was about two orders of magnitude more potent than the isomer with 1R-2 alpha-2'S configuration. The allosteric potencies were found not to be correlated with their competitive binding potencies.
authors.affiliation: Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Z G
authors.initials: ZG
authors.lastname: Gao
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: C G
authors.initials: CG
authors.lastname: Liu
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D008297:Male; D019832:N-Methylscopolamine; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism; D013237:Stereoisomerism; D014316:Tritium; D014326:Tropanes / Q000378:metabolism*
chemical_list: D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D014326:Tropanes; D014316:Tritium; C094207:2-(2'-cyclopentyl-2'-phenyl-2'-hydroxyethoxy)tropane; D019832:N-Methylscopolamine