Mexrenoate potassium: a steroidal aldosterone antagonist and antihypertensive

Mexrenoate potassium (SC-26714) is a water soluble salt of a steroidal hydroxy acid which has been shown to antagonize the sodium-retaining effects of aldosterone at oral dosages of 1 mg/kg and about 1.8 mg/kg in the dog and rat, respectively. Dose-related natriuretic responses, indexed as a reversal (increases) in the aldosterone-depressed urinary log Na/K ratio, indicated that mexrenoate was between 2.1 (dog) and 4.5 (rat) times as potent as spironolactone. Based on sodium output, in intact rats, mexrenoate was essentially inactive as a diuretic with an estimated potency of less than 0.4% that of hydrochlorothiazide. Diuretic potency was not indicative of antihypertensive potency. In dogs with established hypertension (Page model with the remaining kidney decapsulated and cellophane wrapped) both mexrenoate and spironolactone exhibited equivalent antihypertensive responses. An optimum oral dose of either compound was 5 mg/kg/day. Initial and maximum antihypertensive responses were observed on the 2nd and 5th days of treatment, respectively. Recovery to pretreatment hypertensive levels was observed 72 hours later. Mexrenoate shares with spironolactone the pharmacological characteristics of an aldosterone antagonist.