THE DIURETIC EFFECTS OF LARGE DOSES OF ACETAZOLAMIDE AND AN ANALOG LACKING CARBONIC ANHYDRASE INHIBITING ACTIVITY *

Abstract

Intravenous injection of 500 mg/kg of sodium acetazoleamide in dogs produced a massive but transient diuresis in which as much as 40 to 60% of the filtered Na and water and 25 to 50% of the filtered chloride were diverted into the urine. Bicarbonate reabsorption was depressed by 40 to 85% from control rates and the rate of excretion reached 70 to 95% of the filtered load. A substantial part of this effect is probably not explained by inhibition of carbonic anhydrase, because the Na salt of the N2-methyl analogue of acetazoleamide (CL 8490), which has virtually no carbonic anhydrase inhibiting activity in vivo or in vitro, was found to produce a similar though somewhat smaller diuresis. The data indicate that the diuretic action shared by the Na salts of acetazoleamide and CL 8490 cannot be explained on the basis either of the osmotic activity of the administered drugs or their extracellular alkalinizing effects. In view of the size of the dose required and of the transiency of the effect, it is proposed that the shared mechanism of action depends on some temporary alteration in renal cell composition. It is tentatively suggested that depression of electrolyte reabsorption may result from transient intracellular alkalosis produced by cellular accumulation of the monobasic form of the drug.