Anti-adrenocortical activity of SKF 12185 and SKF 252 A.
The synthesis of aldosterone and 18-hydroxycorticosterone from triated corticosterone by sheep adrenal homogenate have been studied in presence of increasing concentrations of SKF 12185, a product already known as an inhibitor of cortisol synthesis. An approximately 98% inhibition of the synthesis of both steroids occurred with only 2 x 10(-4) M of the drug. In contrast, incubation of a structurally closely related compound (SKF 252 A) under the same experimental conditions resulted in an only 52% inhibition with higher concentrations (2 x 10(-3) M). These findings could explain the marked aldosterone fall that occurs in SKF 12185 treated subjects and supports the therapeutic use of this product in treatment of hyperaldosteronism.