Hemodynamic Profile of BM 14.478: A New Positive Inotropic and Vasodilating Agent

BM 14.478 (7,7-dimethyl-2-(4-pyridyl)-6,7-dihydro-3 H, 5H pyrrolo [2,3-f]benz-imidazol-6-one) was investigated in anesthetized rats and cats and conscious dogs. Left ventricular dp/dt was increased after intravenous injection of 0.01–0.1 mg/kg in rats (7,200 ± 300 to 10,700 ± 500 mm Hg/s), 0.001–0.3 mg/kg in cats (2,800 ± 200 to 4,500 ± 100 mm Hg/s) and 0.01 ± 3.0 mg/kg in dogs (2,400 ± 100 to 4,400 ± 500 mm Hg/s). The inotropic potency was about 5- to 18-fold higher than that of milrinone. Effects persisted for more than 6.5 h in dogs after administration of 1 mg/kg p.o., which was definitely longer than that of milrinone. Hypotension and a moderate tachycardia were observed in the same dose range. In conscious dogs the compound increased cardiac output by 39 ± 10%, and stroke volume by 17 ± 7% and lowered total peripheral resistance by 45 ± 5% and right atrial pressure by 3.0 ± 0.3 mm Hg. BM 14.478 induced no tolerance after repeated administration in dogs when administered in a dose of 1 mg/kg p.o. b.i.d. for 10 days.