Pharmacological Studies with Polythiazide, a New Diuretic and Antihypertensive Agent.

Abstract

Polythiazide was found to be a highly potent, orally active diuretic agent in rats and dogs. Duration of polythiazide action was prolonged. The diuretic effect was demonstrated as late as 12 to 24 hours after oral administration of the drug. Onset of polythiazide action was rapid. After intravenous administration to dogs, the maximal saluretic effect was obtained in 10 to 20 minutes. The onset of action after oral administration was less than one hour; maximal effect was obtained either during the first or second hour. Polythiazide produced an almost equal increase in excretion of sodium and chloride. The increase in excretion of potassium was approximately 1/10 of that of sodium. In acute experiments on rats polythiazide was found to be 10 times more potent than trichlormethiazide in its natriuretic effect but only 0.4 times as potent in its kaliuretic effect. Polythiazide at dose levels as high as 10 mg/kg i.v. did not depress glomerular filtration rate. Polythiazide is a carbonic anhydrase inhibitor in vitro. In vivo, polythiazide produced no or only minimal increases in excretion of bicarbonate in animals with normal acid-base balance. The drug was effective as saluretic agent in dogs with experimental metabolic acidosis or alkalosis. Antihypertensive activity of polythiazide was clearly demonstrated in rats and dogs with experimental hypertension. The antihypertensive effect had a slow onset and became evident on the second day of treatment.