Bumepidil

In anesthetized, open-chest dogs 8-tert.-butyl-7,8-dihydro-5-methyl-6H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-a]pyrimidine (CS-611), in doses of 0.1--1 mg/kg i.v. decreased systemic blood pressure, coronary resistance and arterio-venous O2 difference and increased coronary sinus outflow in a dose-related manner, but myocardial oxygen consumption was virtually unchanged. At 0.3 mg/kg i.v. of the drug, coronary sinus outflow was doubled, but heart rate and AV conduction time were not changed. In canine isolated, blood-perfused heart preparations, CS-611 only in large intra-arterial doses produced the following responses; a decrease in sinus rate followed by a slight increase in the SA node preparation, a transient prolongation of AV conduction time followed by a slight shortening in the AV node preparation and a transient decrease followed by a sizable increase in developed tension in the papillary muscle preparation. The drug in large intra-arterial doses decreased the rate of automaticity of the papillary muscle preparation. From these results CS-611 can be characterized as a coronary dilator virtually devoid of cardiac actions in doses sufficiently increasing coronary blood flow. By comparison of the present results with those of previous results on other coronary dilators it was revealed that CS-611 may have a novel mechanism of action.