title: 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.
abstract: 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.
authors.forename: Toshio
authors.initials: T
authors.lastname: Obata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Aomine
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D010624:Phenelzine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D004965:Estrogen Antagonists; D013629:Tamoxifen; D017665:Hydroxyl Radical; D010624:Phenelzine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine