BLOCKING THE RENAL ELECTROLYTE EFFECTS OF MINERALOCORTICOIDS WITH AN ORALLY ACTIVE STEROIDAL SPIROLACTONE

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Abstract
Aldactone, or 3-(3-oxo-7α-acetylthio-l7β-hydroxy-4-androsten-17α-yl)propionic acid γ-lactone, blocked the urinary electrolyte effects of desoxycorticosterone acetate in rats, by simultaneously reversing sodium retention and potassium loss. The compound was ¼ as active parenterally and 5 times as active orally relative to an early steroidal spirolactone, SC-8109 or 3-(3-o×o-17β3-hydroxy-19-nor-4-androsten-17αyl) propionic acid γ-lactone, which has received clinical trials in edematous states and other conditions characterized by aldosteronism. Aldactone was approximately as active orally as parenterally, and it also reversed the urinary electrolyte effects of aldosterone and hydrocortisone. The compound was inactive when given alone. All evidence favors the view that the compound affects electrolyte excretion by competitive inhibition with aldosterone-like steroids at the renal level. The compound did not show cortisone-like, androgenic, anabolic, estrogenic or progestational activity; it was similarly inactive in inhibiting the effects of standard steroids in the endocrinologic tests. The studies indicate that the compound possesses an oral potency which may be useful for the treatment of edema.