THE PTERIDINE WY-3654 AND ITS RELATIONSHIP TO SOME OTHER DIURETIC AGENTS

¹ Pharmacological Evaluation Section, Research Division, Wyeth Laboratories, Inc., Radnor, Pennsylvania

The pteridine diuretic Wy-3654 was given intravenously to unanesthetized dogs undergoing mannitol-plus-phosphate or saline infusions in combination with mercaptomerin, hydrochlorothiazide, and acetazolamide, all at maximally effective diuretic doses. When Wy-3654 was administered with either hydrochlorothiazide or acetazolamide, the excretion of sodium and chloride was additive, but potassium was not, indicating that Wy-3654 blocks tubular sodium and chloride reabsorption at a different site or by a different mechanism than either hydrochlorothiazide or acetazolamide but can interfere with potassium excretion caused by these compounds. Wy-3654 and the organomercurial mercaptomerin, however, were not additive with respect to sodium and chloride reabsorption in either mannitol-plus-phosphate or saline infusion experiments. Renal hemodynamics were shown not to be a critical factor in the inability of the pteridine and organomercurial to be additive; hence, these two drugs probably act on sodium and chloride reabsorption by a similar renal mechanism. Ethacrynic acid was able to elicit a potent saluretic and kaliuretic response when superimposed upon combinations of either Wy-3654 and mercaptomerin or hydrochlorothiazide and mercaptomerin.