Electrocardiographic changes in rats during chronic treatment with antidepressant and neuroleptic drugs.

Five antidepressants, 3 phenothiazines and 5 butyrophenone neuroleptics were administered to rats orally at maximally tolerated doses for 22 weeks. The electrocardiogram (ECG) was recorded weekly. In animals treated with antidepressants quinidine-like changes of the atrioventricular and intraventricular conduction developed. There were also elevation of T-wave and right rotation of the electrical axis. Dibenzepine had the least effect on the ECG. In the group of phenothiazines chlorpromazine induced tachycardia and thioridazine widening of the QRS complex. Prothipendyl had no effect. ECG-changes induced by some of the butyrophenone derivatives were tachycardia and widening of the QRS-complex. In rats treated with protriptyline the ECG changes were correlated with drug concentrations in serum and myocardial tissue. The studies provided a quantitative assessment of the cardiac effects of clinically proven psychotropic drugs. They will be useful as a baseline for the preclinical evaluation of new derivatives.