PT  - JOURNAL ARTICLE
AU  - Hofmann, L M
AU  - Chinn, L J
AU  - Pedrera, H A
AU  - Krupnick, M I
AU  - Suleymanov, O D
TI  - Potassium prorenoate: a new steroidal aldosterone antagonist.
DP  - 1975 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 450--456
VI  - 194
IP  - 2
4099  - http://jpet.aspetjournals.org/content/194/2/450.short
4100  - http://jpet.aspetjournals.org/content/194/2/450.full
SO  - J Pharmacol Exp Ther1975 Aug 01; 194
AB  - 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.