Nakayama H, Nakayama T, Carnes C A, Strauch S M, Hamlin R L
Department of Veterinary Biosciences, The Ohio State University, 1900 Coffey Road, Columbus, Ohio, 43210-1092, USA.
Toxicol Appl Pharmacol. 2001 Dec 1;177(2):157-61. doi: 10.1006/taap.2001.9297.
Apomorphine is a dopamine receptor agonist used as an emetic, for Parkinson's disease, and for treating erectile dysfunction. This study was conducted to monitor cardiovascular function in dogs given the standard emetic dose (0.05 mg/kg) or 10 times that. Measurements were made during baseline and at 1, 5, 15, 30, 45, and 60 min after iv administration. There were no changes produced by the 0.05 mg/kg dose of apomorphine except for a decrease in mean systemic arterial pressure (AoPm) at the 1 through 15 min recordings. For the 0.5 mg/kg dose, there were reductions in systemic vascular resistance at the 1 and 5 min recordings and in AoPm at the 1 through 60 min recordings. Although not significant, when AoPm fell, heart rate, stroke volume, and cardiac output tended to increase. Action potentials were recorded from superfused Purkinje and endocardial ventricular fibers while exposed to 10(-9) to 10(-5) M apomorphine (10(-10) M is considered therapeutic and 10(-7) M is considered lethal). There were no changes in action potential characteristics of Purkinje fibers, but action potential duration at 90% repolarization prolonged approximately 10-12% in endocardium at concentrations of 10(-6) M and greater. At the usual emetic dose (0.05 mg/kg) apomorphine resulted in no signs of cardiovascular toxicity and, at 0.5 mg/kg, cardiovascular changes were minimal. The emetic dose is higher than that for Parkinson's disease or erectile dysfunction; thus apomorphine appears to be a safe compound for clinical use in dogs and by extrapolation to man.
阿扑吗啡是一种多巴胺受体激动剂，用作催吐剂、治疗帕金森病以及治疗勃起功能障碍。本研究旨在监测给予标准催吐剂量（0.05mg/kg）或该剂量10倍的犬的心血管功能。在静脉给药后的基线以及给药后1、5、15、30、45和60分钟进行测量。0.05mg/kg剂量的阿扑吗啡除了在1至15分钟记录时平均体动脉压（AoPm）降低外，未产生其他变化。对于0.5mg/kg剂量，在1和5分钟记录时全身血管阻力降低，在1至60分钟记录时AoPm降低。尽管不显著，但当AoPm下降时，心率、每搏量和心输出量有增加的趋势。在暴露于10（-9）至10（-5）M阿扑吗啡（10（-10）M被认为是治疗剂量，10（-7）M被认为是致死剂量）时，从灌流的浦肯野纤维和心室内膜纤维记录动作电位。浦肯野纤维的动作电位特征没有变化，但在浓度为10（-6）M及更高时，心内膜90%复极化时的动作电位时程延长约10 - 12%。以通常的催吐剂量（0.05mg/kg），阿扑吗啡未导致心血管毒性迹象，而在0.5mg/kg时，心血管变化最小。催吐剂量高于治疗帕金森病或勃起功能障碍的剂量；因此，阿扑吗啡似乎是一种对犬临床使用安全的化合物，通过推断对人类也安全。
