Acute cardiovascular toxicity of trazodone, etoperidone and imipramine in rats

The cardiovascular effects of trazodone, a broad-spectrum antidepressant and its analogue etoperidone, were compared with imipramine, following intravenous infusion in rats. Their effects on electrocardiogram and blood pressure were simultaneously recorded until cardiac arrest. Hypotension was the primary effect of trazodone and etoperidone. ECG changes, i.e. lengthening of the PR interval, were observed only when the blood pressure reached very low values. On the other hand, imipramine produced first the well known ECG changes and then a drop in blood pressure. As far as mortality was concerned, trazodone was the least toxic drug, followed by etoperidone, whereas imipramine was most toxic; these differences being in agreement with the LD50 values reported in rats by the i.v. route. It is concluded that trazodone and etoperidone produce in rats cardiovascular effects, which are different from those of imipramine. Moreover these differences are consistent with their pharmacological properties, particularly their interaction with catecholamines, which are inhibited by trazodone or etoperidone and potentiated by imipramine.