Narita H, Yabana H, Kikkawa K, Miyazaki K, Ikeo T, Nagao T
Jpn J Pharmacol. 1986 Jul;41(3):335-44. doi: 10.1254/jjp.41.335.
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.
我们研究了多巴胺丁胺与儿茶酚胺类药物相比，在犬体内与其正性肌力作用相关的致心律失常活性。以能使麻醉犬左室dp/dt max增加至对照值100%的ED100（微克/千克，静脉注射）来表示，各化合物的正性肌力活性分别为：多巴胺丁胺8.0、去甲肾上腺素0.27、异丙肾上腺素0.03、多巴酚丁胺3.8、多巴胺16。另一方面，在冠状动脉结扎犬中，使“非窦性/总心率”显著增加（约占总搏动数的30%，微克/千克，静脉注射）时，多巴胺丁胺的剂量超过1000，去甲肾上腺素和异丙肾上腺素为1.0，多巴酚丁胺和多巴胺为300。这些剂量与ED100的比值，多巴胺丁胺大于126，多巴酚丁胺为80，异丙肾上腺素为33，多巴胺为19，去甲肾上腺素为3.8。在氟烷麻醉的犬中，多巴胺丁胺的致心律失常活性也弱于多巴酚丁胺和多巴胺。多巴酚丁胺的致心律失常活性如报道的那样较弱，但多巴胺丁胺在受试药物中致心律失常活性最弱。
