Inhibition of alcohol dehydrogenase by chloral hydrate and trichloroethanol: possible role in the chloral hydrate-ethanol interaction.
Both chloral hydrate and trichloroethanol inhibited mouse liver alcohol dehydrogenase (LADH) in vitro. The inhibition of LADH by chloral hydrate appears to be non-competitive in nature with an inhibition constant (Ki) of about 2.7 X 10(-4) M. The inhibition of LADH by trichloroethanol was competitive and the (Ki) was about 2.7 X 10(-5) M. The elimination of ethanol from the blood and brain was significantly reduced in chloral hydrate- or trichloroethanol-pretreated mice. Since reduced elimination of ethanol could result in the prolongation of its central depressant activity, we suggest that this should be considered as a factor in the enhanced pharmacological effects of ethanol-chloral hydrate mixtures.
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001667:Binding, Competitive; D002697:Chloral Hydrate / Q000633:toxicity*; D002728:Chlorohydrins / Q000633:toxicity*; D000431:Ethanol / Q000633:toxicity; D005023:Ethylene Chlorohydrin / Q000031:analogs & derivatives / Q000633:toxicity*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D011187:Posture; D012018:Reflex / Q000187:drug effects
D002728:Chlorohydrins; D000431:Ethanol; D002697:Chloral Hydrate; D005023:Ethylene Chlorohydrin; C005849:2,2,2-trichloroethanol; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase