Studies on the biochemical aspects of the 'disulfiram-like' reaction induced by oral hypoglycemics.
In vitro experiments, using rat liver homogenates, were designed to examine certain of the proposed enzymatic mechanisms for the interaction of oral hypoglycemic drugs with monoamine and ethanol metabolism. The oxidative degradation of tryptamine was studied by measuring indoleacetic acid (IAA) production and conclusions were drawn with regard to the activity of monoamine oxidase, aldehyde dehydrogenase and ethanol dehydrogenase. Acetohexamide, hydroxyhexamide, tolazamide, tolbutamide and chlorpropamide failed to reveal any specific inhibition of the three enzymes. Ethanol (0.2% w/v) and disulfiram decreased IAA formation, as did a lack of available aldehyde dehydrogenase and NAD, but these reductions were not enhanced by the hypoglycemic agents. The results suggest that the 'disulfiram-like' reaction which occurs in certain patients imbibing ethanol while receiving oral hypoglycemic drugs, depends upon some factor(s) other than, or additional to, a specific interference with monoamine and/or ethanol metabolism.
D000284:Administration, Oral; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D004221:Disulfiram / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D007210:Indoleacetic Acids / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D014363:Tryptamines / Q000378:metabolism
D007004:Hypoglycemic Agents; D007210:Indoleacetic Acids; D014363:Tryptamines; D009243:NAD; D000431:Ethanol; D000429:Alcohol Oxidoreductases; D000445:Aldehyde Oxidoreductases; D008995:Monoamine Oxidase; D004221:Disulfiram