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.

01 Jan 1981·Arzneimittel-Forschung

Cardiovascular pharmacology of bumepidil, a new synthetic vasoactive compound for coronary circulation.

Article

Author: Miyake, S ; Nishino, H ; Shimada, Y ; Mizuno, H ; Kumakura, S ; Koike, H ; Oshima, T

Intravenously administered 8-tert.-butyl-7,8-dihydro-5-methyl-6H-pyrrolo[3,2-e]triazolo[1,5-alpyrimidine (bumepidil, CS-611) increased the coronary sinus outflow as well as intramyocardial flows in both subendocardial and subepicardial layers in the anesthetized dog and also the increase in the coronary arterial inflow was observed with short onset time, within 10 min when given orally to the conscious dog, and time for maximum effect is also short, i.e., 20 min after the oral administration. In the anesthetized rabbit flow-increase in the brain by CS-611 was next to the coronary, followed by the stomach and small intestines while there was no organ which showed a decreased flow. In the anesthetized open-chest dog cardiac output was increased by CS-611 while myocardial oxygen consumption was little affected. In addition, CS-611 exerted antiarrhythmic action on ventricular ectopics induced by coronary ligation of the conscious dog. A correlation between the increase in myocardial flow by CS-611 in the intact heart and the antiarrhythmic action in the coronary-lighted heart still remains to be studied further.

01 Aug 1980·Journal of Medicinal ChemistryQ1 · MEDICINE

Studies on cardiovascular agents. 6. Synthesis and coronary vasodilating and antihypertensive activities of 1,2,4-triazolo[1,5-a]pyrimidines fused to heterocyclic systems

Q1 · MEDICINE

Article

Author: Fujita, Hiroshi ; Kobayashi, Shinsaku ; Mizuno, Hiroshi ; Nishino, Hiroshi ; Shimoji, Yasuo ; Sato, Yasunobu ; Kumakura, Seiji

The synthesis and coronary vasodilating and antihypertensive activities of 1,2,4-triazolo[1,5-a]pyrimidines fused to pyrrole, thiophene, pyran, pyridine, and pyridazine are described. Among these compounds, 8-tert-butyl-7,8-dihydro-5-methyl-6H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-a]pyrimidine (23) was found to be the most promising potential cardiovascular agent, having been shown to be more potent in coronary vasodilating activity than trapidil [7-diethylamino)-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine] and approximately equipotent to guanethidine sulfate in antihypertensive activity.

100 Deals associated with Bumepidil

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Indication	Highest Phase	Country/Location	Organization	Date
Cardiovascular Diseases	Discovery	Japan	Daiichi Sankyo Co., Ltd.	-

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