Inotropic and chronotropic activity of a new cardiotonic agent, DM 9278 (1,2,3,4,8,9,10,12-octahydro(2,1-b)pyrido(2,3-f)qunazolin-9-one), on isolated dog atrial and ventricular muscles.

The cardiac effects of DM9278 were studied in isolated and blood-perfused atrial and ventricular preparations from mongrel dogs. In spontaneously beating isolated right atria, DM9278 caused positive chronotropic and inotropic responses in a dose-related manner (1-100 micrograms). DM9278 produced relatively larger positive inotropic than positive chronotropic effects as compared with effects of aminophylline or papaverine. DM9278 increased the developed tension in left ventricles electrically driven at 1.5-2.0 Hz. Positive inotropic and chronotropic responses to DM9278 in both atrial and ventricular preparations were suppressed slightly but not significantly by 1-3 micrograms of propranolol, which completely blocked the positive chronotropic and inotropic effects of norepinephrine (0.01-0.1 micrograms). From these results, it is concluded that DM9278 has direct cardiotonic properties in isolated dog heart tissues, showing relatively selective positive inotropic activity.