Protective effect of tamoxifen, a synthetic non-steroidal antiestrogen, on phenelzine and 1-methyl-4-phenylpyridinium ion (MPP+)-induced hydroxyl radical generation in rat striatum.
The present study examined whether tamoxifen could suppress antidepressant drug phenelzine can increase an active dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+)-induced hydroxyl radical (*OH) generation in the extracellular fluid of rat striatum, using in vivo microdialysis system. Rats were anesthetized, and sodium salicylate (0.5 nmol/microl/min) was infused through a microdialysis probe to detect the generation of *OH as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. Infusion of phenelzine (0.1 mM or 0.1 nmol/microl/min) into the striatum drastically increased dopamine (DA) efflux and the *OH formation, trapped as 2,3-DHBA by the possible increased production of MPP+. However, tamoxifen (100 microM) significantly suppressed phenelzine enhanced DA efflux and *OH formation by MPP+. These results in the pressent study is the first demonstration showing the protective effect of tamoxifen on *OH generation induced by phenelzine enhanced MPP+ by suppressing DA efflux.
Department of Analytical Chemistry, Ohu University School of Pharmaceutical Sciences, Koriyama, Fukushima 963-8611, Japan.
Toshio
T
Obata
Masahiro
M
Aomine
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001596:Benzylamines / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010624:Phenelzine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012980:Sodium Salicylate / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology*
D000928:Antidepressive Agents; D000970:Antineoplastic Agents; D001596:Benzylamines; D002396:Catechols; D020847:Estrogen Receptor Modulators; D062385:Hydroxybenzoates; D013629:Tamoxifen; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; C030796:benzylamine; D006631:Amine Oxidase (Copper-Containing); D010624:Phenelzine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D012980:Sodium Salicylate