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Toxicology and Applied Pharmacology 2001-Dec

Electrophysiologic and hemodynamic effects of apomorphine in dogs.

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H Nakayama
T Nakayama
C A Carnes
S M Strauch
R L Hamlin

Keywords

Abstract

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.

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