Studies with the optically active isomers of the new diuretic drug ozolinone. II. Inhibition by d-ozolinone of furosemide-induced diuresis.

The effect of the non-diuretic dextrorotatory isomer of ozolinone on furosemide-induced diuresis was studied by means of clearance and micropuncture techniques in rats. After intravenous injection, d-ozolinone antagonized the furosemide-induced increase in renal fluid and electrolyte excretion in a dose-related manner. Microperfusion experiments of Henle's loop in vivo revealed that d-ozolinone did not interfere with the action of furosemide at this tubular site. However, d-ozolinone markedly decreased the furosemide to inulin clearance ratio, presumably as a consequence of inhibition of furosemide secretion into the proximal tubules. It is assumed that, in consequence of a high affinity for the proximal organic acid transport system, d-ozolinone depresses proximal tubular furosemide secretion and prevents transfer of this diuretic to the tubular fluid. Thus, under the influence of d-ozolinone, furosemide cannot reach the loop of Henle in sufficient amounts and its diuretic effect is blocked.