Abstract
(-)-Trans-epsilon-viniferin (epsilon-viniferin, 5-200 microM), a dimer of resveratrol, concentration-dependently inhibited the uptake of [3H]noradrenaline and [3H]5-HT by synaptosomes from rat brain (being slightly but significantly more selective against [3H]noradrenaline) and the uptake of [3H]5-HT by human platelets. On the other hand, epsilon-viniferin (5-200 microM) concentration-dependently inhibited the enzymatic activity of commercial (human recombinant) monoamine oxidase (MAO) isoform (MAO-A and MAO-B) activity, being slightly but significantly more selective against MAO-B than against MAO-A. Taking into account that the principal groups of drugs used to treat major depression are noradrenaline/5-HT uptake or MAO inhibitors, under the assumption that epsilon-viniferin exhibits a similar behaviour in humans in vivo, our results suggest that this natural polyphenol may be of value as a structural template for the design and development of new antidepressant drugs with two important biochemical activities combined in the same chemical structure: noradrenaline/5-HT uptake and MAO inhibitory activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzofurans / chemistry
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Benzofurans / pharmacology*
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Blood Platelets / drug effects
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Blood Platelets / metabolism
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Brain / drug effects*
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Brain / metabolism
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Cell Line
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Citalopram / pharmacology
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Clorgyline / pharmacology
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Dose-Response Relationship, Drug
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Fluoxetine / analogs & derivatives
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Fluoxetine / pharmacology
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Humans
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Imipramine / pharmacology
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Iproniazid / pharmacology
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Male
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Monoamine Oxidase / genetics
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Monoamine Oxidase / metabolism
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Monoamine Oxidase Inhibitors / pharmacology*
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Norepinephrine / pharmacokinetics*
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / metabolism
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Selegiline / pharmacology
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Serotonin / pharmacokinetics*
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Stilbenes / chemistry
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Stilbenes / pharmacology*
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Synaptosomes / drug effects
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Synaptosomes / metabolism
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Tritium
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Wine*
Substances
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Benzofurans
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Isoenzymes
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Monoamine Oxidase Inhibitors
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Recombinant Proteins
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Stilbenes
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Fluoxetine
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Citalopram
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Tritium
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nisoxetine
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Selegiline
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Serotonin
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epsilon-viniferin
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Iproniazid
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Monoamine Oxidase
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Clorgyline
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Imipramine
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Norepinephrine