(-)-Trans-epsilon-viniferin, a polyphenol present in wines, is an inhibitor of noradrenaline and 5-hydroxytryptamine uptake and of monoamine oxidase activity.
(-)-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.
Yáñez
Matilde
M
Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Universitario Sur, E-15782 Santiago de Compostela (La Coruña), Spain.
Fraiz
Nuria
N
Cano
Ernesto
E
Orallo
Francisco
F
D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D015283:Citalopram / Q000494:pharmacology; D003010:Clorgyline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D007490:Iproniazid / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000493:pharmacokinetics*; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014316:Tritium; D014920:Wine
D001572:Benzofurans; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D011994:Recombinant Proteins; D013267:Stilbenes; D005473:Fluoxetine; D015283:Citalopram; D014316:Tritium; C011386:nisoxetine; D012642:Selegiline; D012701:Serotonin; C091891:epsilon-viniferin; D007490:Iproniazid; D008995:Monoamine Oxidase; D003010:Clorgyline; D007099:Imipramine; D009638:Norepinephrine