PMID: 2504998Aug 1, 1989Paper

Effect of the benzodiazepines diazepam, des-N-methyldiazepam and midazolam on corticosteroid biosynthesis in bovine adrenocortical cells in vitro; location of site of action

Journal of Steroid Biochemistry
C D HollowayR Fraser

Abstract

Diazepam and midazolam inhibited cortisol and aldosterone synthesis in bovine adrenal cells in vitro. The biologically active metabolite des-N-methyldiazepam did not. Midazolam was a more potent inhibitor (IC50: 6 micrograms/ml) than diazepam (IC50: 13 micrograms/ml) in ACTH-stimulated cells. Both compounds inhibited steroidogenesis at several points in the biosynthetic chain; the greatest effects were on 17 alpha hydroxylation and 21 hydroxylation. Diazepam had a relatively greater effect on 17 alpha hydroxylation; midazolam on 21 hydroxylation. Both were less potent inhibitors of 11 beta hydroxylation and had little apparent effect on side chain cleavage. Thus microsomal hydroxylation is more vulnerable to benzodiazepines than mitochondrial hydroxylation. It is suggested that the drugs act by competing with steroid mixed function oxidases for cytochrome P-450. The plasma concentrations required for these effects are high in relation to therapeutic levels but may be achieved, for example, during acute infusions or when they are used in combination with imidazole drugs such as cimetidine.

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Citations

Jun 1, 1991·The Journal of Steroid Biochemistry and Molecular Biology·I ThomsonC J Kenyon
Jun 1, 1995·The Journal of Steroid Biochemistry and Molecular Biology·I ThomsonC J Kenyon
Jun 1, 1995·The Journal of Steroid Biochemistry and Molecular Biology·V Papadopoulos, A S Brown
Feb 19, 1999·Anaesthesia·G NicholsonG M Hall
May 5, 1999·Fundamental & Clinical Pharmacology·C J KenyonR Fraser
Jun 1, 1993·Acta Physiologica Scandinavica·S MatzenJ Warberg
Mar 19, 2014·Annales Françaises D'anesthèsie Et De Rèanimation·E BesnierV Compère
Feb 9, 1996·Biochemical Pharmacology·D M Stocco, B J Clark
Dec 17, 2016·Anesthesia and Analgesia·Emmanuel BesnierVincent Compere
Sep 30, 2020·The Journal of Steroid Biochemistry and Molecular Biology·Malene Louise JohannsenBjarne Styrishave
Oct 1, 1992·Molecular and Cellular Endocrinology·M GavishR Weizman
Oct 28, 2009·Toxicology Letters·Edmund Cheung SoBu-Miin Huang

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