Chlorpromazine and ethanol intoxication: an underlying mechanism.
The in vitro effect of chlorpromazine on hepatic alcohol dehydrogenase (L-ADH) was studied as a function of sex and species. The presence of chlorpromazine, 50 muMol, in reaction mixture noncompetitively inhibited rat L-ADH in a dose dependent fashion in the concentration range between 5 X 10(-5) Mol and 10(-4) Mol. This drug concentration also inhibited L-ADH of albino mice of both sexes, but chlorpromazine-produced a decrease in Km which was greater in the female than in the male mouse. Likewise, chlorpromazine, 50 muMol, noncompetitively inhibited mouse L-ADH of C57BL/6J, a mouse strain with ethanol preference, but without a concomitant change in the apparent Km. The KI50 determination indicates 3.5 fold lower concentration requirement of the drug in the C57BL mouse strain compared to that of the albino rat liver preparation. The results suggest that the inhibitory action of the drug on L-ADH and the genetic factor involved may influence the legal limit of serum ethanol concentration during alcohol intoxication in subjects under psychotropic medications. A medical forensic implication is suggested.
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000435:Alcoholic Intoxication / Q000097:blood; D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D000431:Ethanol / Q000097:blood; D005260:Female; D005554:Forensic Medicine; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D051381:Rats; D012737:Sex Factors; D013045:Species Specificity
D000431:Ethanol; D000429:Alcohol Oxidoreductases; D002746:Chlorpromazine