Inhibitory effect of drugs with a ketone group on reduction of acetohexamide catalyzed by carbonyl reductase from rabbit kidney.
The reduction of acetohexamide catalyzed by carbonyl reductase from rabbit kidney was inhibited by befunolol, moperone, levobunolol, daunorubicin and loxoprofen, which have a ketone group within their chemical structures and are substrates for the enzyme. A significant correlation was observed between the common logarithm of Vmax/Km values of the enzyme for befunolol, moperone, levobunolol and daunorubicin and the percentage inhibition of the enzyme, confirming that these drugs are competitive substrates of the enzyme with respect to acetohexamide. However, the plot for loxoprofen, a nonsteroidal anti-inflammatory drug with a ketone group, was apparently distant from the regression line obtained. Although nonsteroidal anti-inflammatory drugs with a ketone group such as suprofen and fenbufen were not reduced by the enzyme, they strongly inhibited the reduction of acetohexamide catalyzed by the enzyme.
Imamura
Y
Y
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Koga
T
T
Higuchi
T
T
Otagiri
M
M
Sugino
E
E
Hibino
S
S
D000092:Acetohexamide / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002090:Butyrophenones / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007659:Ketones / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D002040:Levobunolol / Q000494:pharmacology; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010666:Phenylpropionates / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011817:Rabbits; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002090:Butyrophenones; D004791:Enzyme Inhibitors; D007659:Ketones; D010666:Phenylpropionates; D011412:Propanolamines; C040656:loxoprofen; C006034:befunolol; D000429:Alcohol Oxidoreductases; D002040:Levobunolol; C005209:moperone; D000092:Acetohexamide; D003630:Daunorubicin