The antabuse reaction, seen in patients imbibing alcohol while being treated with an antidiabetic sulfonylurea, is thought to be due to either an increase in acetaldehyde levels or an alteration in the metabolism of serotonin. Both can occur through an inhibition of aldehyde dehydrogenase. The oral antidiabetic sulfonylureas, chlorpropamide and tolbutamide, were found to be noncompetitive inhibitors of this enzyme. Acetaldehyde, a metabolite of ethanol, can competitively inhibit aldehyde dehydrogenase. Moreover, the oxidation of ethanol reverses the DPN/DPNH ratio so that the favored pathway of serotonin metabolism is altered, resulting in a decrease of 5-hydroxyindoleacetic acid (5-HIAA) and an increase of 5-hydroxytryptophol. Thus, ethanol augments the action of the sulfonylureas. Whether the syndrome results from an accumulation of acetaldehyde due to a block in ethanol metabolism, or whether it is a result of an alteration in the metabolism of serotonin, the noncompetitive inhibition of aldehyde dehydrogenase by the sulfonylureas, coupled with the actions of ethanol, may be considered as a potential cause.

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