THE PHARMACOLOGICAL ACTIVITIES OF BENZTHIAZIDE (3-BENZYLTHIOMETHYL-6-CHLORO-7-SULFAMYL-1,2,4-BENZOTHIADIAZINE-1,1-DIOXIDE), A NONMERCURIAL DIURETIC

¹ Macrobiology Research and Chemical Research Departments, Research Division, Chas. Pfizer & Co., Groton, Connecticut

Benzthiazide is an orally effective and highly potent nonmercurial diuretic and saluretic. In comparison with chlorothiazide, it is 4 and 8 times more potent in dogs and rats, respectively, in increasing urine flow, and approximately 7 and 16 times more potent in the same animals, respectively, in increasing the excretion of sodium and chloride.

When compared with hydrochlorothiazide in rats benzthiazide was found to be slightly (1.8 times) more potent in its natriuretic effect.

Although benzthiazide is an active carbonic anhydrase inhibitor in vitro, in vivo studies suggest that the saluretic effect of this compound is based primarily on an action other than carbonic anhydrase inhibition.

Daily oral administration of massive doses of benzthiazide to dogs over an extended period did not cause any significant change of plasma electrolytes.

Benzthiazide is of a low order of toxicity. Daily oral administration of 1 and 5 g/kg was well tolerated by rats and dogs for a period of 3 months or longer.