Comparative in vitro and in vivo studies on the effects of tricyclic antidepressants on myocardial contractility.

The effects of the similarily structured antidepressant drugs imipramine and dimetacrine and their demethylated derivatives on myocardial performance were studied in vitro on 42 right ventricular papillary muscles of cats. The hemodynamic effects of intravenous administration of 22 mg of free base imipramine and dimetacrine were investigated in 12 patients with coronary disease. The results of the in vitro studies show that imipramine greater than dimetacrine greater than desmethyl compounds have a marked dose-dependent negative inotropic effect on all parameters of myocardial contractility, i.e., afterloaded isotonic contractions (delta L), dL/dtmax, dL/dtmin,dT/dt. The hemodynamic investigations indicate that imipramine greater than dimetacrine induces a significant increase in end-diastolic left ventricular pressure. Both drugs increase mean arterial blood pressure, correlated to a peripheral vasoconstriction and corresponding to an increase on the plasma level of catecholamines. It is concluded that both effects of these antidepressant drugs (reduction of myocardial performance and an increase in the plasma level of catecholamines) must be considered a risk in patients predisposed to myocardial failure.