Cardiovascular properties of a new cardiotonic agent: MDL 17,043 (1.3-dihydro-4-methyl-5-[4-(methylthio)-benzoyl]-2H-imidazol-2-one).

The cardiovascular properties of a new noncatechol, nonglycoside cardiotonic agent, MDL 17.043, were investigated in anesthetized and conscious dogs and the dog heart-lung preparation. MDL 17.043 (0.1–1 mg/kg), administered to anesthetized dogs by intravenous injection, produced dose-related increases in cardiac contractile force lasting more than 1 h. It also produced relatively minor and shorter-lasting increases in heart rate, and brief, decreases in blood pressure. These effects were not blocked by propranolol. Of these effects, the increase in cardiac contractile force was, by far, the most prominent. The cardiac effects were also observed in the dog heart-lung preparation. When administered to anesthetized dogs by constant intravenous infusion. MDL 17.043 (0.03 and 0.1 mg/kg/min) produced a marked and sustained increase in cardiac contractile force and a sustained decrease in blood pressure without altering heart rate, suggesting a wide separation between the inotropic and chronotropic effects of this drug. Given orally to conscious, chronically instrumented dogs. MDL 17.043 (3–30 mg/kg) produced a sustained increase in dP/dt without altering heart rate or blood pressure. It reversed the depressant effect of pentobarbital on the ventricular function curve in the dog heart-lung. When the hemodynamic characteristics of compensated heart failure were produced by propranolol in anesthetized dogs. MDL 17.043 reversed these effects. These studies suggest that MDL 17.043 may have a beneficial effect in the treatment of heart failure.