The Mechanism of Mineralocorticoid Action of Carbenoxolone*

Abstract

The principal side effects of the drug carbenoxolone (Biogastrone; 18β-glycyrrhetinic acid sodium hemisuccinate) are sodium retention, hypokalemic alkalosis, suppressed plasma renin, and hypertension. In previous animal studies, carbenoxolone appeared not to have intrinsic mineralocorticoid activity but, rather, to enhance aldosterone action by displacing it from nonspecific binding sites. We here report studies showing that carbenoxolone has demonstrable affinity for rat kidney mineralocorticoid receptors, intrinsic mineralocorticoid activity in the adrenalectomized rat at doses consistent with its receptor affinity, and, in addition, a powerful action of amplifying the electrolyte effects of near-maximal doses of aldosterone.