PMID: 38088May 1, 1979

Formation of two metyrapone N-oxides by rat liver microsomes

Drug Metabolism and Disposition : the Biological Fate of Chemicals
J De GraeveB Maume

Abstract

In the presence of phenobarbital-pretreated rat liver microsomes and under oxidative conditions, metyrapone is transformed in vitro into reduced metyrapone and two other metabolites. In an effort to further characterize those metabolites, large-scale incubations of metyrapone were performed. Untransformed substrate and metabolites were extracted into chloroform under alkaline conditions and separated by thin-layer chromatography. The nature of the metabolites as N-oxides located on either pyridine ring was established by physical methodologies, mainly electron-impact and chemical-ionization mass spectrometry, and also by chemical reactions with titanous chloride. The formation of both N-oxides was increased in microsomes from phenobarbital-, but not from 3-methylcholanthrene-pretreated animals. N-Oxide formation during metyrapone metabolism might be an important step in its inhibitory action on the cytochrome P-450-mediated drug metabolism.

Related Concepts

SU 4885
Cyclic N-Oxides
Methylcholanthrene
Microsomes, Liver
Mass Spectrometry
NADP
Luminal

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