Hemodynamic profile of N-(2,5-dimethyl-1H-pyrrol-1-yl)6-(4-morpholinyl)-3-pyridazinamine hydrochloride in conscious dogs.

The effects of N-(2,5-dimethyl-1H-pyrrol-1-yl)6-(4-morpholinyl)-3-pyridazinamine hydrochloride (MDL-899) on systemic, pulmonary, renal and coronary circulation and on myocardial contractility have been investigated in conscious dogs treated orally. The compound induced a decrease in systemic arterial blood pressure, slow in onset (peak effect at 4 h) and long-lasting (more than 7 h), by reducing total peripheral resistance, while the heart rate, cardiac output, cardiac work and myocardial contractility increased because of the reflex increase in sympathetic drive evoked by the blood pressure fall. Coronary and renal blood flows were increased for a long time. Pulmonary resistance was markedly decreased, but the pulmonary pressure was increased, probably due to the hyperkinetic activity triggered by the increases of cardiac output and heart rate. The hemodynamic changes induced by MDL-899 are qualitatively similar to those induced by hydralazine. The results suggest that the compound belongs to the class of vasodilators that act primarily on systemic arterioles to produce arteriolar dilation.