EFFECTS OF IBOPAMINE ON SYSTEMIC, PULMONARY AND REGIONAL HEMODYNAMICS - EXPERIMENTAL INVESTIGATIONS IN ANESTHETIZED DOGS

Abstract

The effects of a new orally effective dopamine-like derivative, ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, on the cardiovascular system were investigated in anesthetized dogs. Ibopamine increased dose-dependently stroke volume index, cardiac index, left ventricular pressure, its first derivative: dP/dt, peak velocity left ventricular ejection and renal blood flow. After .beta.-blockade the positive inotropic effect of ibopamine is inhibited. Total peripheral resistance and renal vascular resistance decreased after ibopamine. Urine output was increased dose-dependently, reaching 115% after ibopamine 8 mg/kg intraduodenally. Coronary and femoral flows and resistance did not change after administration of 4 and 8 mg/kg. Only very high doses (24 mg/kg) caused an increase in flow and resistance. Mesenteric flow decreased transiently and then returned to the previous level or increased considerably over the basal figures when a high dose was used. No significant changes or fall in heart rate were observed with doses up to 16 mg/kg and no significant changes in pulmonary resistance were noted. The data obtained from the present investigation show, however, that oral ibopamine is capable of producing most of the effects induced by intravenously given dopamine in anesthetized dogs. Ibopamine''s cardiac and renal effects may open new prospects for the long-term treatment of chronic heart failure in human subjects.