The inhibition of 11β-hydroxylation of deoxycorticosterone by metopirone in bovine adrenal perfusions

Abstract Deoxycorticosterone (DOC), 125 mg/l, 3.8 × 10 −4 M, in bovine blood was perfused, through bovine adrenal glands in the presence of a varying amount of Metopirone (100-3.15 mg/l, 4.4−0.14 × 10 −4 M) and for a varying number of cycles (5–35) to determine whether 11β-hydroxylation to corticosterone would be inhibited by Metopirone in this system and whether DOC would be shunted into other metabolic pathways. With Metopirone at 100-25 mg/l, the inhibition of 11β-hydroxylation was essentially complete in the standard 5-cycle perfusion and was almost complete even after 30 cycles. At 3.15 mg/l,the inhibition was still about 65% effective after 5 cycles and about 30% effective after 22 cycles. The general metabolism of DOC in other directions was slowed. With Metopirone at 100 mg/l, 84% of the DOC was recovered after 5 cycles. At 3.15 mg/l, the recovery was still about 40%. However, 13 metabolites other than corticosterone were isolated from the various perfusates, all in conversions of 3% or less. Five substances were identified. Of these, 6β-hydroxy-DOC was formed even within 5 cycles with Metopirone at 100 mg/l. Neither this substance nor the 8 unidentified compounds have been isolated from non-inhibited perfusions.