Biogenic aldehyde(s) derived from the action of monoamine oxidase may mediate the antidipsotropic effect of daidzin

Daidzin, a major active principle of an ancient herbal treatment for 'alcoh ol addiction', was first shown to suppress ethanol intake in Syrian golden hamsters. Since then this activity has been confirmed in Wistar rats, Fawn hooded rats, genetically bred alcohol preferring P rats and African green m oneys under various experimental conditions, including two-level operant, t wo-bottle free-choice, limited access, and alcohol-deprivation paradigms. I n vitro, daidzin is a potent and selective inhibitor of mitochondrial aldeh yde dehydrogenase (ALDH-2). However, in vivo, it does not affect overall ac etaldehyde metabolism in golden hamsters. Using isolated hamster liver mito chondria and 5-hydroxytryptamine (5-HT) and dopamine (DA) as the substrates , we demonstrated that daidzin inhibits the second but not the first step o f the MAO/ALDH-2 pathway, the major pathway that catalyzes monoamine metabo lism in milochondria. Correlation studies using structural analogs of daidz in led to the hypothesis that the mitochondrial MAO/ALDH-2 pathway may be t he site of action of daidzin and that one or more biogenic aldehydes such a s 5-hydroxyindole-3-acetaldehyde (5-HIAL) and/or DOPAL derived from the act ion of monoamine oxidase (MAO) may be mediators of its antidipsotropic acti on. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.