
INHIBITION BY CYANIDE OF DRUG OXIDATIONS IN RAT LIVER MICROSOMES
Author(s) -
Munehiro Kitada,
Kazuhiro Chiba,
Tetsuya Kamataki,
Haruo Kitagawa
Publication year - 1977
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.27.601
Subject(s) - cyanide , ethylmorphine , chemistry , cytochrome , hydroxylation , microsome , dissociation constant , aniline , stereochemistry , drug , enzyme , biochemistry , pharmacology , organic chemistry , biology , receptor
Cyanide inhibited microsomal activities of aniline hydroxylation and aminopyrine, ethylmorphine and codeine demethylations and produced a modified type II difference spectrum of cytochrome P-450 to give two spectral dissociation constants, 0.21mM and 1.05 mM. The binding of cyanide to cytochrome P-450 resulted in innhibition of NADPH-cytochrome P-450 reductase activity. The cyanide inhibition of drug oxidations was partially avoided by increasing oxygen tension. A possible mechanism for the inhibition of drug oxidations by cyanide is discussed.