Weak arrhythmogenic property of the new cardiotonic agent denopamine in dogs: comparison with catecholamines.
We studied the arrhythmogenic activity of denopamine, in relation to its positive inotropic action, in dogs and compared it with those of catecholamines. The positive inotropic activities of the compounds as expressed in terms of the ED100 (microgram/kg, i.v.), that increased LV dp/dt max of anesthetized dogs by 100% of the control were 8.0 for denopamine, 0.27 for norepinephrine, 0.03 for isoproterenol, 3.8 for dobutamine and 16 for dopamine. On the other hand, the doses of these drugs at which the "non-sinus/total rate" increased significantly (about 30% of total beats, microgram/kg, i.v.) were more than 1000 for denopamine, 1.0 for norepinephrine and isoproterenol, and 300 for dobutamine and dopamine in coronary ligated dogs. The ratios of these doses to the ED100 are more than 126 for denopamine, 80 for dobutamine, 33 for isoproterenol, 19 for dopamine and 3.8 for norepinephrine. Arrhythmogenic activity of denopamine was also weaker than those of dobutamine and dopamine in halothane anesthetized dogs. The arrhythmogenic activity of dobutamine was weak as reported, but that of denopamine was the weakest among the drugs tested.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D002316:Cardiotonic Agents / Q000633:toxicity*; D002319:Cardiovascular System / Q000187:drug effects; D002395:Catecholamines / Q000633:toxicity; D004280:Dobutamine / Q000633:toxicity; D004285:Dogs; D004983:Ethanolamines / Q000494:pharmacology / Q000633:toxicity*; D006221:Halothane / Q000633:toxicity; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000633:toxicity
D002316:Cardiotonic Agents; D002395:Catecholamines; D004983:Ethanolamines; D004280:Dobutamine; D007545:Isoproterenol; D006221:Halothane; C037293:denopamine