A comparison of the effects produced by metyrapone and its reduced metabolite on the adrenal 11β-hydroxylase system in the rat

A comparison of the effects of metyrapone* and its major metabolite (SU-5236) upon adrenocortical steroid 11β-hydroxylation has been carried out. When either compound was added to rat adrenal mitochondria in vitro, significant inhibition of corticosterone production was apparent. The spectral change induced by the reduced metabolite was identical to that produced by metyrapone. Similarly, both compounds substantially reduced the magnitude of the 11-deoxycorticosterone-induced difference spectrum. These same effects were demonstrable in adrenal mitochondria following the administration of either compound to rats in vivo. In each case, the inhibitory effects of SU-5236 were nearly as great as those of metyrapone itself, indicating that the conversion of metyrapone to this metabolite cannot account for the inactivation of this potent inhibitor of 11β-hydroxylation.