MEXRENOATE POTASSIUM - STEROIDAL ALDOSTERONE ANTAGONIST AND ANTIHYPERTENSIVE

  • 1 January 1977
    • journal article
    • research article
    • Vol. 201  (3) , 762-768
Abstract
Mexrenoate potassium (SC-26714) is a water soluble salt of a steroidal hydroxy acid which antagonized the Na 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 Na 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 per 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 h later. Mexrenoate shares with spironolactone the pharmacological characteristics of an aldosterone antagonist.