title: The effects of AF-DX 116, a cardioselective muscarinic antagonist, on the negative inotropic action of acetylcholine.
abstract: In superfused left atria from male guinea pigs, rats, and rabbits, myocardial contractility was measured before and after addition of acetylcholine (ACh) and AF-DX 116 ((11[[2-[(diethylamino)methyl]-1-piperidinyl]-acetyl]-5,11-dihydro- 6H-pyrido[2,3-b] [1,4]benzodiazepine-6-) one), a selective muscarinic antagonist. Characteristic dose-response curves for acetylcholine showing greater negative inotropic response with dose were seen. Increasing AF-DX 116 concentrations reversed the negative inotropy of acetylcholine and, in fact, increased the inotropic response approximately 100% and 50% above the baseline contractile force in a dose-dependent manner in the guinea pig and rabbit, respectively. This increase in contractility following AF-DX 116 addition was not observed in rat atria. The capacity of AF-DX 116 to produce the positive inotropic response only occurred at concentrations above 1 x 10(-5) M. The positive inotropic response of AF-DX 116 was antagonized by dl-propranolol, which suggests that the administration of AF-DX 116 at higher concentrations may unmask the effect of norepinephrine released from underlying viable adrenergic terminals which exist in the left atria.
authors.affiliation: United States Army Medical Research Institute of Chemical Defense, SGRD-UV-PB, Aberdeen Proving Ground, MD 21010-5425.
authors.forename: S I
authors.initials: SI
authors.lastname: Baskin
authors.forename: R H
authors.initials: RH
authors.lastname: Thomsen
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010890:Pirenzepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology
chemical_list: D011976:Receptors, Muscarinic; D010890:Pirenzepine; D011433:Propranolol; D000109:Acetylcholine; C048593:otenzepad