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.
D015069:18-Hydroxycorticosterone / Q000378:metabolism; D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000311:Adrenal Glands / Q000187:drug effects*; D000450:Aldosterone / Q000096:biosynthesis; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D003864:Depression, Chemical; D066298:In Vitro Techniques; D010627:Phenethylamines / Q000494:pharmacology*; D011335:Proadifen / Q000494:pharmacology*; D012756:Sheep
D000814:Aniline Compounds; D010627:Phenethylamines; D000450:Aldosterone; D015069:18-Hydroxycorticosterone; D011335:Proadifen; D003345:Corticosterone