The effect of tricyclic antidepressant drugs on the heart

Summary The effects on the heart rate and ECG of anaesthetised guinea-pigs of amitriptyline, doxepin, imipramine and nortriptyline infused at 1.0 mg/kg/min until death were observed. In addition an in vitro study on guinea-pig atria was performed on the chronotropic and inotropic effects of these drugs and of desmethylimipramine and protriptyline at a concentration of 10^–5 M. The effect of sodium bicarbonate (3 mEq/kg i.v.) and propranolol (0.01–0.2 mg/kg i.v.) on amitriptyline and doxepin induced ECG changes was also assessed.A difference in the cardiac effects of the in vivo and in vitro model was observed. Guinea-pigs infused with doxepin survived significantly longer than those infused with amitriptyline, imipramine or nortriptyline. No statistically significant difference was found between the tricyclic drugs with respect to onset of widening of the QRS complex, increased PR and QT intervals. In the spontaneously beating atrial preparation doxepin was the most potent cardio-depressant. Sodium bicarbonate had no effect on arrhythmias induced by tricyclics, while propranolol, apart from the bradycardia induced, was without beneficial effect on the ECG.The guinea-pig provides a good model for studying the arrhythmogenic actions of tricyclic antidepressants.This paper was presented in part at the 9th Annual Meeting of the Australasian Society for Clinical and Experimental Pharmacologists in Melbourne on November 27, 1975