The Problem of Bioassay and Comparative Potency of Diuretics

AS THE uses for diuretic agents have multiplied because of a greater understanding of the pathologic physiology of salt and water metabolism, a fertile field for the development of new agents that will increase the excretion of sodium and water has developed. Diuretics may be categorized according to their mechanisms of action.' The most commonly used diuretic agents are, of course, the organomercurials and these are available for parenteral injection as well as oral use. The parenteral forms are used in markedly edematous states and the oral mercurials find wide usefulness for maintenance therapy. The mechanism of action of the mercurial compounds has been reported to be the inhibition of succinic dehydrogenase activity in Henle's loop of the nephron.2 Second only in importance to the mercurial diuretics are the agents that promote the excretion of sodium and water by the inhibition of carbonic anhydrase activity in the distal convoluted tubule of the nephron.3 In general, these are sulfonamide derivatives that may be administered orally to assist the control of mild edema. The purpose of the present study is to report the method for the bioassay of carbonic anhydrase inhibitors as diuretic agents with the result that the comparative potency of these agents may be established. The 4 drugs to be compared are all sulfonamide derivatives and