Narcan inhibition of human liver alcohol dehydrogenase.
Narcan, the pharmaceutical agent for the administration of naloxone, has been reported to antagonize ethanol intoxication. In addition to naloxone, Narcan contains the antioxidant esters methyl- and propylparaben. Pure naloxone and these two esters were examined for their capacity to inhibit ethanol oxidation by purified isozymes of human liver alcohol dehydrogenase (ADH). Naloxone (400 micromolar) fails completely to inactivate any of the three ADH isozyme classes. In contrast, methyl- and propylparaben, and some related esters, competitively inhibit the oxidation of ethanol and reduction of acetaldehyde by all isozymes examined. The reported effects of Narcan on ethanol-intoxicated animals or cells cannot be attributed to the action of naloxone.
Dingley
A L
AL
Holmquist
B
B
Vallee
B L
BL
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001667:Binding, Competitive; D004952:Esters; D000431:Ethanol / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D009270:Naloxone / Q000494:pharmacology*; D010226:Parabens / Q000494:pharmacology
D004952:Esters; D007527:Isoenzymes; D010226:Parabens; C012313:ethyl-p-hydroxybenzoate; D009270:Naloxone; D000431:Ethanol; C015358:methylparaben; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; C006068:propylparaben