Cardiovascular actions of 5,6-dimethoxy-2-(3-[(alpha-(3,4-dimethoxy) phenylethyl)-methylamino] propyl) phthalimidine (AQ-A 39), a specific bradycardic agent.
1. v. administration of 5,6-dimethoxy-2-(3-[(alpha-(3,4-dimethoxy) phenylethyl) methylamino] propyl)- phthalimidine (AQ-A 39) to anaesthetized animals induced dose dependents bradycardia. A comparison of the cardiovascular actions of AQ-A 39 to those of the chemically related Ca2+-antagonist verapamil in anaesthetized cats revealed that AQ-A 39 reduced heart rate more that arterial blood pressure of left ventricular dpldtmax, whereas verapamil was more active in decreasing blood pressure and myocardial contractility that in reducing heart rate. The corresponding ED20% (mg/kg i.v.) for AQ-A 39 were 0.5 (heart rate), 2.9 (mean arterial blood pressure) and 1.8 (dp/dt max). The respective ED20% for verapamil were 1.2, 0.06 and 0.08 mg/kg i.v. Decrease in dp/dt max following injection of AQ-A 39 but not of verapamil could be abolished or diminished by cardiac pacing. So the inotropic effect following i.v. administration of AQ-A 39 were mainly due to interval-strength relationship. Cardiac output was much less decreased than heart rate since there was a significant increase in stroke volume in both anaesthetized cats and dogs. Peripheral resistance was not significantly influenced by systemic administration of AQ-A 39. In anaesthetized dogs AQ-A 39 (0.5 and 2.0 mg/kg i.v.) reduced myocardial oxygen consumption without impairing cardiac work output (i.e., mean aortic pressure X cardiac output). AQ-A 39 induces cardiovascular actions which might be of benefit in the treatment of ischaemic heart disease.
D000818:Animals; D002317:Cardiovascular Agents; D002415:Cats; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D054833:Isoindoles; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010797:Phthalimides / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D014700:Verapamil / Q000494:pharmacology
D002317:Cardiovascular Agents; D054833:Isoindoles; D010797:Phthalimides; D014700:Verapamil; C030532:falipamil