The effect of pargyline and other monoamine oxidase inhibitors on blood acetaldehyde levels in ethanol-intoxicated mice.
Pargyline (100 mg/kg i.p.) administered to Swiss-Webster mice prior to the injection of ethanol (4 g/kg i.p.) elevated blood acetaldehyde levels to a mean of 20 mug/ml, compared to less than 1 mug/ml in control mice treated with ethanol alone. Elevated blood acetaldehyde was observed when ethanol was given at 15 minutes, 2 or 5 hours after pargyline; the action of pargyline had largely disappeared after 18 hours. The magnitude of the increase in blood acetaldehyde levels was dependent upon the dose of pargyline between 20 and 100 mg/kg; however, the elevation was relatively independent of the ethanol dose between 1 and 6 g/kg. Of the other monoamine oxidase inhibitors tested, Lilly 51641 showed a strong elevation in acetaldehyde (mean 13.3 mug/ml), whereas deprenyl and clorgyline gave modest elevations (2.9 and 2.6 mug/ml, respectively), and nialamide and tranylcypromine were only weakly active (1.4 and 1.2 mug/ml, respectively). Blood acetaldehyde levels in mice treated with pargyline and ethanol were strongly depressed (85%) by pyrazole, an inhibitor of alcohol dehydrogenase, and moderately to strongly depressed (49-71%) by pretreatment with phenobarbital, an inducer of liver aldehyde dehydrogenase.
D000079:Acetaldehyde / Q000097:blood*; D000435:Alcoholic Intoxication / Q000097:blood*; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010293:Pargyline / Q000494:pharmacology*; D013997:Time Factors
D008996:Monoamine Oxidase Inhibitors; D000431:Ethanol; D010293:Pargyline; D000445:Aldehyde Oxidoreductases; D000079:Acetaldehyde