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-3H,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.