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Cardiovascular Actions of DPI 201–106, a Novel Cardiotonic Agent

Summary: DPI 201–106 (4-[3-(4-diphenylmethyl-1-piperazinyl)-2-hydroxypropoxy]-1 H-indole-2-carbonitrile) is characterized by a marked cardiotomic activity. The compound exerted positive inotropic effects in anesthetized and conscious dogs, pithed open-chest cats, and isolated hearts of cardiomyopathic hamsters and vanadate-treated guinea-pig atria. Left ventricular dP/dtmax was increased in anesthetized dogs after i.v. injection of 0.2 and 2 mg/kg DPI 201–106 (34 ± 6 and 104 ± 18%, respectively) and in unanesthetized dogs after oral doses of 2–8 mg/kg (22 ± 3 to 50 ± 5%, respectively). In most experiments, the compound lowered blood pressure and heart rate. Stroke work and left ventricular work were almost unaffected by DPI 201–106, and oxygen consumption and cardiac efficiency remained unchanged in open-chest dogs. Studies of the mechanism of action of DPI 201–106 lead to the conclusion that its positive inotropic effect is not explainable either by β-stimulation or by liberation of catecholamines. This was shown in anesthetized dogs and pithed open-chest cats pretreated with propranolol and reserpine.