THE NATRIURETIC ACTION OF DT-327

¹ Department of Pharmacology, Michigan State University, East Lansing, Michigan

DT-327 is an orally effective natriuretic-diuretic in man and laboratory animals. The natriuretic action of this chemically unique diuretic was studied after i.v. administration in anesthetized dogs. DT-327 produced a prompt increase in urine flow and excretion of sodium, potassium and chloride with no significant alteration in inulin or PAR clearance. The drug produced a small increase in bicarbonate excretion but did not signiticantly alter plasma or urinary pH. Marked diuresis continued for at least 90 min after a single i.v. injection of 1 mg/kg. Increasing doses of DT-327 were administered during mannitol diuresis. The natriuretic response observed was dose-related between 0.01 and 1 mg/kg. The drug produced a significant reduction in free water clearance but had no effect on negative free water clearance. During maximal natriuresis produced by hydrochlorothiazide, DT-327 had no effect on sodium excretion. Conversely, after a maximally effective dose of DT-327, hydrochlorothiazide was without effect. However, these experimental animals were still capable of responding to furosemide. Thus it appeared that DT-327, although chemically not a thiazide, could produce a relatively specific blockade of the action of a thiazide diuretic. It is concluded that the natriuretic action of DT-327 is not unique but closely resembles the thiazides.