ArticleAlcohol and alcoholism (Oxford, Oxfordshire)
Tryptophan in alcoholism treatment I: kynurenine metabolites inhibit the rat liver mitochondrial low Km aldehyde dehydrogenase activity, elevate blood acetaldehyde concentration and induce aversion to alcohol.
Article in Alcohol and alcoholism (Oxford, Oxfordshire). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 29 citations in OpenAlex.
- Alcohol Use Disorder and the Gut-Brain Axis: A Narrative Review of the Role of Gut Microbiota and Implications for Treatment.Microorganisms · 2025Review
- Influx of kynurenine into the brain is involved in the reduction of ethanol consumption induced by Ro 61-8048 after chronic intermittent ethanol in mice.British journal of pharmacology · 2022Article
- Alterations of kynurenine pathway in alcohol use disorder and abstinence: a link with gut microbiota, peripheral inflammation and psychological symptoms.Translational psychiatry · 2021Article
- Changes in brain kynurenine levelsFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Kynurenic acid and alcohol and cocaine dependence: novel effects and multiple mechanisms?Psychopharmacology · 2017Article
- Reply to: kynurenic acid and alcohol and cocaine dependence: novel effects and multiple mechanisms?Psychopharmacology · 2017Article
- Elevation of Kynurenine Metabolites in Rat Liver and Serum: A Potential Additional Mechanism of the Alcohol Aversive and Anti-cancer Effects of Disulfiram?Alcohol and alcoholism (Oxford, Oxfordshire) · 2016Article
- Tryptophan Metabolism in Rat Liver After Administration of Tryptophan, Kynurenine Metabolites, and Kynureninase Inhibitors.International journal of tryptophan research : IJTR · 2016Article
- Tryptophan metabolism, disposition and utilization in pregnancy.Bioscience reports · 2015Review
- A mathematical model of tryptophan metabolism via the kynurenine pathway provides insights into the effects of vitamin B-6 deficiency, tryptophan loading, and induction of tryptophan 2,3-dioxygenase on tryptophan metabolites.The Journal of nutrition · 2013Article
- Aldehyde dehydrogenase inhibitors: a comprehensive review of the pharmacology, mechanism of action, substrate specificity, and clinical application.Pharmacological reviews · 2012Review
- Tryptophan in alcoholism treatment II: inhibition of the rat liver mitochondrial low Km aldehyde dehydrogenase activity, elevation of blood acetaldehyde concentration and induction of aversion to alcohol by combined administration of tryptophan and benserazide.Alcohol and alcoholism (Oxford, Oxfordshire)Article
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsThe aims were to provide proofs of mechanism and principle by establishing the ability of kynurenine metabolites to inhibit the liver mitochondrial low K(m) aldehyde dehydrogenase (ALDH) activity after administration and in vivo, and to induce aversion to alcohol.
methodsKynurenic acid (KA), 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HAA) were administered to normal male Wistar rats and ALDH activity was determined both in vitro in liver homogenates and in vivo (by measuring blood acetaldehyde following ethanol administration). Alcohol consumption was studied in an aversion model in rats and in alcohol-preferring C57 mice.
resultsALDH activity was significantly inhibited by all three metabolites by doses as small as 1 mg/kg body wt. Blood acetaldehyde accumulation after ethanol administration was strongly elevated by KA and 3-HK and to a lesser extent by 3-HAA. All three metabolites induced aversion to alcohol in rats and decreased alcohol preference in mice.
conclusionsThe above kynurenine metabolites of tryptophan induce aversion to alcohol by inhibiting ALDH activity. An intellectual property covering the use of 3-HK and 3-HAA and derivatives thereof in the treatment of alcoholism by aversion awaits further development.
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