The effect of ethanol ingestion on serotonin-C14 metabolism in man

Feldstein, Aaron; Hoagland, Hudson; Freeman, Harry; Williamson, Owen Douglas

doi:10.1016/0024-3205(67)90361-x

Cited by 71 publications

(16 citation statements)

References 16 publications

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“…Subsequently, 5-hydroxytryptophol was identified as a serotonin (5-hydroxytryptamine) metabolite in rats (3,4), bovine pineals (5), and humans, both in vivo (6) and in brain tissue in vitro (7). Ethanolinduced modification of the metabolism of biogenic indole amines results in the increased production of tryptophol compounds, specifically 5-hydroxytryptophol (4,(8)(9)(10)(11)(12)(13). Disulfiram (Antabuse, Ayerst Laboratories, New York) treatment in rats induces the formation of tryptophol (14) and increased quantities of 5-hydroxytryptophol (10).…”

Section: Introductionmentioning

confidence: 99%

Rapid distribution of tryptophol (3-indole ethanol) to the brain and other tissues.

Cornford¹,

Bocash²,

Braun³

et al. 1979

J. Clin. Invest.

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A B S T R A C T Tryptophol (3-indole ethanol) is a compound which induces sleep, and is formed: (a) in the liver after disulfiram treatment, and (b) by the parasite in trypanosomal sleeping sickness. We prepared, purified, and characterized radiolabeled tryptophol for the purpose of defining its tissue distribution in animals. Tryptophol was found to be highly lipophilic, with an octanol: water partition coefficient of 29.8. Brain extraction, determined after intracarotid injection, was high (brain uptake index = 117+3.5%), and nonsaturable, suggesting the absence of a carrier system. After intravenous administration, tryptophol distribution to tissues correlated with relative blood flow. More than 85% of the radioactivity remaining in brain 2-5 min after intravenous injection co-migrated with tryptophol standards when analyzed by thin-layer chromatography. Other evidence suggested that tryptophol binds to serum and in vivo may be stripped from serum albumin and taken up by brain in a single capillary transit. Our study suggests that in states such as trypanosomal sleeping sickness or disulfiram treatment, remotely formed tryptophol gains ready access to brain (it is 100% cleared in a single capillary passage), and could thus cause somnolence.

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Section: Introductionmentioning

confidence: 99%

Rapid distribution of tryptophol (3-indole ethanol) to the brain and other tissues.

Cornford¹,

Bocash²,

Braun³

et al. 1979

J. Clin. Invest.

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“…It has been shown that ethanol in humans decreases the urinary excretion of 5-HIAA [Olson el al., 1960;Feldstein et al, 1964Feldstein et al, , 1967 and also the 5-HIAA levels in animals [Rosenfeld 1960;Jofre de Brcyer et al, 1967. Olson [1960] suggested that this ef fect may be due to the depression of tryptophan conversion to 5-IIIAA.…”

Section: Discussionmentioning

confidence: 99%

“…Olson [1960] suggested that this ef fect may be due to the depression of tryptophan conversion to 5-IIIAA. Feldstein et al [1967] have suggested that ethanol in creases NADH and decreases NAD with a subsequent decrease in 5-HIAA levels and increase of those of 5-hydroxytryptophol It has been ¡»Iso reported that acetaldehyde, a product of ethanol catabolism, decreases like ethanol Ihe production of 5-IlIAA Majclirowicz, 1967. 1969] by affecting aldehyde dehydro genase but not MAO.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Aldehydes on Serotonin Metabolism in Rat Liver Slices

Breyer¹,

Ortiz²,

Soehring³

1970

Pharmacology

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“…It has been shown that at least some of the NADdependent oxidative metabolic pathways are adversely affected. For instance, ethanol decreases the production of 5-hydroxyindoleacetic acid from 5-hydroxytryptamine with a concomitant increase in formation of 5-hydroxytryptophol (Davis, Brown, Huff & Cashaw, 1967;Feldstein, Hoagland, Freeman & Williamson, 1967;Feldstein & Sidel, 1969). Other experiments have shown that the oxidative metabolism of catecholamines is likewise modified (Lahti & Majchrowicz, 1969;Walsh, Truitt & Davis, 1970;Bonham Carter, ' Present address: Department of Pharmacology, School of Pharmacy, University of Houston, Houston, Texas 77004, U.S.A. Karoum, Sandler & Youdim, 1970).…”

Section: Introductionmentioning

confidence: 99%

Effect of Ethanol on the Oxidative Metabolism of Tryptamine by Rat Liver Homogenate

Asaad

Barry

Clarke

et al. 1974

British J Pharmacology

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1 The effect of a wide range of ethanol concentrations (v/v) on indoleacetic acid (IAA) formation from the oxidative deamination of tryptamine was studied in vitro, in rat whole liver homogenate. 2 IAA production was inhibited progressively by ethanol in concentrations between 0.01% to 0.2%, but the inhibition declined when the ethanol concentration was increased further to 6%. 3 Ethanol-induced inhibition of IAA formation was only partially reversed by excess aldehyde dehydrogenase, whereas reductions in IAA formation were completely prevented by pyrazole or ethanol (6% and 10%) itself. 4 Excess nicotinamide adenine dinucleotide failed to alter the inhibitory effect of ethanol and no evidence was obtained for inhibition of monoamine oxidase by ethanol or its metabolite, acetaldehyde. 5 We conclude that ethanol indirectly inhibits IAA production as a result of oxidation of ethanol by alcohol dehydrogenase, during which the oxidative metabolism of tryptamine is shifted towards the reductive pathway, thus favouring the formation of tryptophol in place of IAA.

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The effect of ethanol ingestion on serotonin-C14 metabolism in man

Cited by 71 publications

References 16 publications

Rapid distribution of tryptophol (3-indole ethanol) to the brain and other tissues.

Rapid distribution of tryptophol (3-indole ethanol) to the brain and other tissues.

The Effects of Aldehydes on Serotonin Metabolism in Rat Liver Slices

Effect of Ethanol on the Oxidative Metabolism of Tryptamine by Rat Liver Homogenate

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