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.Drugs acting in the central nervous system and in endogenous neurotransmitters can induce DNA damage in brain tissue [1][2][3]. Glutamate is a neurotransmitter capable of inducing excitotoxicity in neurodegenerative diseases like Parkinson and Alzheimer, mediated by release of calcium, which can initiate a cascade of intracellular signals that result in oxidative stress [4,5]. As N-methyl-d-aspartate (NMDA) receptors are mediators in glutamate-induced neurodegeneration, one line of therapeutic research has been focused on the development of non-competitive NMDA receptor antagonists that would block the undesired elevations of Ca +2 caused by the prolonged action of glutamate in the extracellular space, without interfering with glutamate physiological actions required for learning and memory [6][7][8][9].Aminoadamantanes represent a class of drugs that block NMDA glutamate receptors and have already been used clinically as antiviral and anti-parkinsonian agents. Some of these drugs are known to have a neuroprotective effect in animal models [10][11][12][13]. Memantine is a neuroprotective aminoadamantane, which blocks NMDA receptor in a noncompetitive fashion. It has been reported that memantine increases brain-derived neurotrophic factor levels [14,15] and synaptic plasticity in the aged rat [16], protects neurons from glutamate-induced neurotoxicity [17,18] and reduces b-amyloid-induced apoptotic death and neuroinflammation in the hippocampus [19].There are few studies on the effects of aminoadamantane drugs on genomic stability. A recent study has shown genotoxic effects of amantadine assessed by comet assay in blood and brain tissues of mice [3]. In this study, we evaluated the possible genotoxic ⁄ antigenotoxic...