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Journal of Pharmacology And Experimental Therapeutics, Vol. 136, Issue 3, 344-352, 1962
Copyright © 1962 by American Society for Pharmacology and Experimental Therapeutics

PHARMACOLOGY OF DIAZOXIDE, AN ANTIHYPERTENSIVE, NONDIURETIC BENZOTHIADIAZINE

Alan A. Rubin 1, Franklin E. Roth 1, Richard M. Taylor 1, and Herbert Rosenkilde 1

1 Department of General Pharmacology, Biological Research Division, Schering Corporation, Bloomfield, New Jersey

Diazoxide, a benzothiadiazine analogue, reduced arterial blood pressure in various animal preparations. The drug did not appreciably affect urine or electrolyte excretion in dogs, but depressed both functions in rats. In chronic studies, orally administered diazoxide lowered blood pressure in renal hypertensive dogs and in active DCA or metacorticoid hypertensive rats. Diazoxide also prevented the development of DCA-hypertension in rats.

In acute studies, intravenous injections of diazoxide caused an immediate and prolonged hypotension which was not significantly antagonized by autonomic blocking agents or spinal transection. Following intraarterial injections of diazoxide, the rate of blood flow increased in femoral, renal and coronary vascular beds. Pre- and postganglionic sympathetic nerve function and adrenergic smooth muscle receptor sites were unaffected by this agent as demonstrated in the cat nictitating membrane preparation. Diazoxide nonspecifically antagonized aortic strip contractions in vitro. It is suggested that diazoxide exerts its characteristic hypotensive effect by directly affecting vascular smooth muscle.

Submitted on January 29, 1962




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Copyright © 1962 by the American Society for Pharmacology and Experimental Therapeutics.