title: The allosteric binding profile of himbacine: a comparison with other cardioselective muscarinic antagonists.
abstract: The possibility of an allosteric interaction by himbacine, a cardioselective antagonist, with rat cardiac muscarinic receptors was studied. Himbacine allosterically decelerated the dissociation of bound [3H]N-methylscopolamine [( 3H]NMS) in a concentration-dependent manner with an IC50 value of 103.7 microM. When compared to the IC50 values of other cardioselective antagonists, the rank order of potencies was: methoctramine greater than gallamine greater than himbacine greater than AF-DX 116. In contrast, the potencies of these compounds to displace [3H]NMS binding were: himbacine greater than methoctramine greater than AF-DX 116 greater than gallamine. The allosteric potencies were found not to be correlated with binding potencies (correlation coefficient = -0.15). A striking common feature of the cardioselective antagonists is their ability to bind to an allosteric site on cardiac muscarinic receptors.
authors.affiliation: Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore 21201.
authors.forename: N H
authors.initials: NH
authors.lastname: Lee
authors.forename: E E
authors.initials: EE
authors.lastname: el-Fakahany
mesh_terms: D000470:Alkaloids / Q000378:metabolism*; D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D003959:Diamines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005663:Furans; D005703:Gallamine Triethiodide / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019832:N-Methylscopolamine; D009281:Naphthalenes; D010880:Piperidines; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism
chemical_list: D000470:Alkaloids; D003959:Diamines; D005663:Furans; D009281:Naphthalenes; D010880:Piperidines; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D001285:Atropine; C048172:himbacine; C054938:methoctramine; D005703:Gallamine Triethiodide; D019832:N-Methylscopolamine