Potassium prorenoate: a new steroidal aldosterone antagonist.
Potassium prorenoate (SC-23992) is a water-soluble steroidal compound with the ability to antagonize the sodium-retaining and, when apparent, the potassium-dissipating effects of mineralocorticoids. A significant natriuretic response was obtained at dosages of 1 mg/kg and approximately 1.8 mg/kg in the dog and rat, respectively. Based upon an elevation in the previously depressed urinary log Na/K ratio, prorenoate possesses an oral potency of 4.6 and 8.1 times that of spironolactone (S), respectively, in the aldosterone and deoxycorticosterone acetate-treated adrenalectomized rat. In the aldosterone-treated dog, the compound had 3.0 times the potency of S and 2.2 times that of a related steroid, potassium canrenoate (SC-14266). Prorenoate and S are relatively inactive at the renal level in adrenalectomized rats without mineralocorticoid replacement. Prorenoate possesses no more than 2% of the natriuretic activity of hydrochlorothiazide in the intact animal. Clearance studies in dogs indicate a direct renal tubular site of interaction between prorenoate and aldosterone independent of changes in renal hemodynamics. The natriuretic response occurred within 100 minutes after a single oral dose and was sustained for at least 7 hours. Prorenoate possesses the pharmacological characteristics of an aldosterone antagonist, in common with those of S.
D000311:Adrenal Glands / Q000502:physiology; D000315:Adrenalectomy; D000818:Animals; D002191:Canrenoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D003900:Desoxycorticosterone / Q000037:antagonists & inhibitors; D004232:Diuretics / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D007668:Kidney / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D011188:Potassium / Q000652:urine; D011245:Pregnadienes / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000652:urine; D013148:Spironolactone / Q000494:pharmacology / Q000031:analogs & derivatives
D004232:Diuretics; D000451:Mineralocorticoid Receptor Antagonists; D011245:Pregnadienes; D013148:Spironolactone; D003900:Desoxycorticosterone; D002191:Canrenoic Acid; D012964:Sodium; D011188:Potassium; C010768:prorenoate potassium