Effects of etomidate on steroid biosynthesis in subcellular fractions of bovine adrenals.

The imidazole derivative, etomidate, inhibits the 11 beta-hydroxylase in cell-free systems and mitochondria isolated from bovine adrenal cortex. Fifty per cent inhibition is achieved at 3.10(-7) M. The less active hypnotic L-enantiomer is also a less potent inhibitor of the 11-hydroxylation. At a 2 times higher concentration, etomidate affects the cholesterol side chain cleavage. The inhibition of both steroidogenic enzyme systems may be due to binding of the unhindered nitrogen of the imidazole ring of etomidate to the heme iron atom of the adrenal cortex mitochondrial cytochrome P-450 species.