The inhibition by metopirone of 11β- and 19-hydroxylations of 11-deoxycortisol in bovine adrenal perfusion

Abstract When 11-deoxycortisol, 3.6 × 10 −4 M, was perfused through cow adrenals for 5 cycles, cortisol (55.0% conversion) and 19-hydroxy-11-deoxycortisol (2.1%) were isolated. No precursor was recovered. When this perfusion was repeated in the presence of Metopirone, 1.1 × 10 −4 M, cortisol (0.2%) was obtained and deoxycortisol (63.5%) was recovered. An extension of the latter perfusion to 29 cycles led to the isolation of 17,21-dihydroxy-5α-pregnane-3,20-dione (3.5%), deoxycortisol (31.5%), cortisol (2.5%), 6β-hydroxy-11-deoxycortisol (2.1%) and 19-hydroxy-11-deoxycortisol (0.8%). Four other metabolites were isolated from inhibited perfusions but not identified. Conclusions: Metopirone inhibited 11β- and, probably, 19-hydroxylation but permitted 6β-hydroxylation.