title: The interaction of amitriptyline, doxepin, imipramine and their N-methyl quaternary ammonium derivatives with subtypes of muscarinic receptors in brain and heart.
abstract: The interaction of amitriptyline, doxepin, imipramine and their N-methyl quaternary derivatives with muscarinic receptors was investigated in the brain and heart. The potency of the tricyclic derivatives for inhibiting the binding of 11[[2-[(diethylamino) methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b] [1,4] benzodiazepine-6-one to M2 muscarinic receptors in cerebral cortex was similar to that measured in competitive binding experiments with the nonselective muscarinic antagonist [3H]N-methylscopolamine in the corpus striatum and heart. Moreover, the tricyclic derivatives antagonized muscarinic receptor-mediated inhibition of adenylate cyclase activity with similar potency in the corpus striatum and heart, and there was good agreement between the affinities of the tricyclic derivatives when measured by radioligand binding and by antagonism of the adenylate cyclase response. Our results show that amitriptyline, doxepin and imipramine lack selectivity for subtypes of the muscarinic receptor.
authors.affiliation: Department of Pharmacology, College of Medicine, University of California, Irvine.
authors.forename: F J
authors.initials: FJ
authors.lastname: Ehlert
authors.forename: F M
authors.initials: FM
authors.lastname: Delen
authors.forename: S H
authors.initials: SH
authors.lastname: Yun
authors.forename: H A
authors.initials: HA
authors.lastname: Liem
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D004316:Doxepin / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007099:Imipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D019832:N-Methylscopolamine; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012602:Scopolamine Derivatives / Q000378:metabolism
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D004316:Doxepin; D000639:Amitriptyline; D010890:Pirenzepine; D010095:Oxotremorine; C042743:oxotremorine M; D007099:Imipramine; C048593:otenzepad; D019832:N-Methylscopolamine