Inhibition of adrenocortical, mitochondrial and microsomal monooxygenases by SU-10'603, a steroid 17 alpha-hydroxylase inhibitor.

SU-10'603 is a pyridine derivative that is widely used as a steroid 17 alpha-hydroxylase inhibitor. Studies were done to evaluate its effects in vitro on several other monooxygenases in guinea pig adrenal mitochondrial and microsomal preparations. In adrenal mitochondria, SU-10'603 produced a concentration-dependent inhibition of 11 beta-hydroxylation; 50% inhibition was obtained at a concentration of approximately 0.5 mM. Its potency was similar to that of the 11 beta-hydroxylase inhibitor, metyrapone. SU-10'603 was a more potent inhibitor of cholesterol sidechain cleavage (CSC) than of 11 beta-hydroxylation; a 50% decline in CSC activity was produced by an inhibitor concentration of approximately 0.1 mM. In adrenal microsomal preparations, SU-10'603 had no effect on the rate of 21-hydroxylation of 17 alpha-hydroxyprogesterone. However, SU-10'603 was a potent inhibitor of adrenal microsomal xenobiotic metabolizing monooxygenases (benzo[a]pyrene hydroxylase, benzphetamine demethylase), effecting approximately 50% inhibition of both reactions at a concentration of 0.05 mM. The results indicate that SU-10'603 inhibits several monooxygenases in the guinea pig adrenal cortex and is thus not specific for 17 alpha-hydroxylation.