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Renal effects of metolazone (MET), a new diuretic agent, were compared with those of hydrochlorothiazide (HCT) in rats. MET in an oral dose of 0.01 approximately 0.5 mg/kg resulted in a dose-related increase in urine flow, sodium excretion and osmolal clearance in male rats. The natriuretic action of MET was not enhanced by administration of an increased dosage (1 approximately 5 mg/kg). Urinary excretion of potassium was significantly increased after MET, but was less than that of sodium. Therefore, the ratio of urinary concentration of sodium to potassium was markedly increased. Similar results were obtained when MET was intraperitoneally administered. In female rats, MET also proved to be an effective natriuretic. The diuretic effects of HCT were qualitatively similar to those of MET, but MET was 10--20 times as potent as HCT on a basis of minimal effective dose. In the renal clearance experiments, MET did not influence the renal plasma flow and glomerular filtration rate. From these findings, it is concluded that MET exerts a diuretic effect by inhibiting the reabsorption of electrolytes in the renal tubules.

Pharmacological study on diuretic action of 2-methyl-3-(o-tolyl)-6-sulfamyl-7-chloro-1, 2, 3, 4-tetrahydro-4-quinazolinone (Metolazone).