Studies on the cardiovascular depressant effects of N-ethyl- and N-benzyl-1,2-diphenylethanolamines in the rat: elucidation of the mechanisms of action.

The influence and mechanisms of action of N-ethyl- and N-benzyl-1,2-diphenylethanolamines (compounds E and B, respectively) on the arterial blood pressure and the heart rate of the rat together with their effects on CaCl2-induced arrhythmias in the rat were investigated. Both E and B in doses of (1.5-12 micromol/kg IV) decreased the arterial blood pressure and the heart rate in a dose-dependent manner. Studies with various receptor blockers, enzyme inhibitors and CaCl2 revealed that E-induced cardiovascular depressant effects were mainly due to CaCl2 channel blocking action and activation of cyclic guanylyl cyclase or release of NO whereas the cardiovascular effects of B seemed to involve both blockade of Ca2+ channels and activation of parasympathetic ganglia. Both compounds (12-14.5 micromol/kg) completely protected the rat against CaCl2 (60 mg kg(-1))-induced tachyarrhythmias. The B compound seemed to be several times more potent than the E compound in its cardiovascular depressant actions. The results suggest the potential usefulness of both compounds in the treatment of hypertension and supraventricular arrhythmias.