ALDEHYDE DEHYDROGENASE INHIBITORS

ALDEHYDE DEHYDROGENASE INHIBITORS are agents that block a class of enzymes involved in the second stage of the sequence of enzymes involved in the breakdown of ethanol (conversion of acetaldehyde to acetic acid), inhibition of which results in accumulation of acetaldehyde as a metabolite. There is marked human polymorphism in this enzyme, with marked ethnic-related distributions, generally with lower levels of enzyme activity in the East (e.g. in Chinese and Japanese). Acetaldehyde is more active than ethanol and very toxic, especially to neural tissue and the liver. In the presence of aldehyde dehydrogenase inhibitors, if even only a small amount of alcohol is taken, this gives rise to very unpleasant and potentially dangerous reactions, such as flushing, headache, palpitations, nausea and vomiting. In clinical usage, the aldehyde dehydrogenase inhibitor disulflram can be prescribed to be taken by an alcoholic subject on a regular basis, so there is a powerful disincentive to the consumption of alcoholic beverages (a form of aversion therapy). A number of other chemicals act as aldehyde dehydrogenase inhibitors, including certain industrial chemicals (e.g. thiram (used in rubber vulcanizing), cyanamide, thiocarbamate herbicides, some drugs (e.g. the hypoglycaemic sulphonylureas, metronidazole, certain cephalosporins) and certain experimental compounds including phenethyl isothiocyanate. Aldehyde dehydrogenase is also involved in the degradation of monoamines such as noradrenaline and adrenaline, so aldehyde dehydrogenase inhibitors can also modify monoamine metabolism.