title: Effects of memantine, a non-competitive N-methyl-D-aspartate receptor antagonist, on genomic stability.
abstract: Memantine is an aminoadamantane drug useful in neurodegenerative diseases, with beneficial effects on cognitive functions. Some studies have shown that memantine protects brain cells, thereby decreasing glutamate excitotoxicity. This study evaluated the genotoxic/antigenotoxic and mutagenic effects of memantine in CF-1 mice, following standardized protocols. Memantine was administered i.p. at 7.5, 15 or 30 mg/kg for three consecutive days. Blood and brain samples were collected to assess DNA damage using the alkaline comet assay. The mutagenic effect was assessed using the bone marrow micronucleus test. In addition, possible antioxidant effects were evaluated measuring the survival of Saccharomyces cerevisiae yeast strains [wild-type (WT) and isogenic mutants lacking superoxide dismutase] to cotreatment of memantine plus hydrogen peroxide. Memantine decreased DNA oxidative damage mainly in brain tissue. This antigenotoxic effect corroborated an increase observed in the survival of S. cerevisiae WT strain against hydrogen peroxide-induced damage. Furthermore, memantine did not increase the micronucleus frequency. The overall results indicate that memantine showed no mutagenic activity, did not cause DNA damage in the blood and brain tissues and showed antigenotoxic effects in brain tissue.
authors.affiliation: Laboratório de Genética Toxicológica, Programa de Pós-Graduação em Genética e Toxicologia Aplicada, ULBRA, Canoas, RS, Brazil.
authors.forename: Édina Madeira
authors.initials: ÉM
authors.lastname: Flores
authors.forename: Shandale Emanuele
authors.initials: SE
authors.lastname: Cappelari
authors.forename: Patrícia
authors.initials: P
authors.lastname: Pereira
authors.forename: Jaqueline Nascimento
authors.initials: JN
authors.lastname: Picada
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042822:Genomic Instability / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D051379:Mice; D015162:Micronucleus Tests; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development; D013482:Superoxide Dismutase / Q000172:deficiency
chemical_list: D000975:Antioxidants; D016194:Receptors, N-Methyl-D-Aspartate; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D008559:Memantine