Affiliation:
1. Institute of Pharmaceutical Science, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, Hiroshima 734, Japan
Abstract
Abstract
The reductive debromination of a hypnotic, (α-bromisovaleryl)urea to (3-methylbutyryl)urea by rat liver microsomes was studied.
Pretreatment of rats with cytochrome P450 inducers such as phenobarbitone, 3-methylcholanthrene, acetone and pregnenolone-16α-carbonitrile enhanced the debromination of (α-bromisovaleryl)urea by liver microsomes. Microsomal debromination was inhibited by cytochrome P450 inhibitors such as metyrapone, α-naphthoflavone, SKF 525-A and carbon monoxide. Microsomal debromination was enhanced by addition of NADPH-cytochrome P450 reductase and inhibited by addition of an antibody against the flavo enzyme to the liver microsomes. A reconstituted cytochrome P450 system containing NADPH-cytochrome P450 reductase, and cytochrome P450 1A1 or P450 2B1 exhibited debrominating activity toward the hypnotic.
These results indicated that a cytochrome P450 system plays an essential role in the microsomal debromination of (α-bromisovaleryl)urea.
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
Cited by
5 articles.
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