BLOCKADE OF THE DIURETIC ACTION OF BENZOTHIADIAZINES

¹ Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Ex 4877, a benzothiadiazine with a free sulfamyl group, was nondiuretic when administered to dogs in a dose of 2.5 mg/kg. A mild diuretic response could be elicited at twice this dose level. Even at the lower dose, Ex 4877 given intravenously limited or blocked the response to a subsequent injection of hydrochlorothiazide.

The drug did not completely abolish the diuretic response to chlorothiazide unless maximal carbonic anhydrase inhibition was first achieved by prior administration of acetazolamide. Acetazolamide, itself, retained full diuretic activity when given to animals pretreated with Ex 4877.

It is concluded that Ex 4877 is a potent inhibitor of the chloruretic ("B") effect of benzothiadiazines but does not limit carbonic anhydrase inhibitory ("A") activity. These two effects thus appear to be separable and not interdependent.