Memantine is highly potent in protecting cortical cultures against excitotoxic cell death evoked by glutamate and N-methyl-D-aspartate.

Department of Anatomy, Georg-August-University, Göttingen, F.R.G.
European Journal of Pharmacology (Impact Factor: 2.68). 07/1991; 198(2-3):215-7. DOI: 10.1016/0014-2999(91)90625-Z
Source: PubMed

ABSTRACT The capacity of memantine to protect cultured cerebrocortical cells against N-methyl-D-aspartate (NMDA)- and glutamate-induced cell death was examined. Excitotoxic cell death was evaluated by phase contrast microscopy and quantified by estimating the release of lactic dehydrogenase from damaged cells. Memantine showed a strong, long-lasting and concentration-dependent protective effect against the excitotoxic damage induced by glutamate and NMDA, with almost complete protection being attained at a memantine concentration of 0.1 mM. The present findings indicate that memantine has potential value as a drug against excitotoxic brain damage.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of our investigation was to characterize the role of group I mGluRs and NMDA receptors in pathomechanisms of experimental autoimmune encephalomyelitis (EAE), the rodent model of MS. We tested the effects of LY 367385 (S-2-methyl-4-carboxyphenylglycine, a competitive antagonist of mGluR1), MPEP (2-methyl-6-(phenylethynyl)-pyridine, an antagonist of mGluR5), and the uncompetitive NMDA receptor antagonists amantadine and memantine on modulation of neurological deficits observed in rats with EAE. The neurological symptoms of EAE started at 10-11 days post-injection (d.p.i.) and peaked after 12-13 d.p.i. The protein levels of mGluRs and NMDA did not increase in early phases of EAE (4 d.p.i.), but starting from 8 d.p.i. to 25 d.p.i., we observed a significant elevation of mGluR1 and mGluR5 protein expression by about 20% and NMDA protein expression by about 10% over the control at 25 d.p.i. The changes in protein levels were accompanied by changes in mRNA expression of group I mGluRs and NMDARs. During the late disease phase (20-25 d.p.i.), the mRNA expression levels reached 300% of control values. In contrast, treatment with individual receptor antagonists resulted in a reduction of mRNA levels relative to untreated animals.
    01/2013; 2013:186068. DOI:10.1155/2013/186068
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To evaluate the effects of memantine on improving visual function in patients with acute nonarteritic anterior ischemic optic neuropathy (NAION) Methods: This was a prospective, double masked, randomized, clinical trial. The study involved 47 subjects with unilateral NAION of less than 8 weeks duration. Eligible patients were randomly allocated to take either memantine tablets (5 mg daily during the first week and then 10 mg daily for the next two weeks, 25 subjects) or placebo tablets (22 subjects). Baseline visual acuity (VA) tests, pattern visual evoked potential (VEP) and automated perimetry (SITA-standard 24-2) were performed. VA tests were repeated 3 weeks, 3 months and 6 months after initial visit. VEP and automated perimetry were repeated 3 months after initial visit. Results: At baseline there was no significant difference between the two groups in terms of clinical and laboratory characteristics. After 3 weeks, 3 months and 6 months of treatment, best corrected visual acuity (BCVA) improved by -0.31±0.39, -0.49±0.47 and -0.53±0.48 logMAR in the memantine group respectively and -0.02±0.41, -0.09±0.60 and -0.05±0.67 logMAR in the placebo group respectively (P=0.024, P=0.025 and P=0.017). VEP results demonstrated a reduction of implicit time of -8.32±17.18 ms in the memantine group after 3 months, whereas in the placebo group it increased +5.7±21.60 ms (P=0.043). The change in VEP amplitude was not significantly different between the memantine and placebo groups (P=0.083). The effect of the memantine on mean deviation (MD) and pattern standard deviation (PSD) changes was not significantly different from that of the placebo (P=0.428 and 0.863 respectively). Conclusion: Treatment of patients who experience acute NAION with memantine may result in significant improvement in BCVA compared with no treatment. The VEP changes seen at 3 months may indicate improved transmission of impulses through the optic nerve. Keywords: Automated Perimetry, Memantine, Nonarteritic Anterior Ischemic Optic Neuropathy, Visual Evoked Potential
    Iranian Journal of Ophthalmology 01/2011; 23(1):11-20. · 0.09 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Neuropharmacology research in glutamate-modulating drugs supports their development and use in the management of neuropsychiatric disorders, including major depression, Alzheimer's disorder and schizophrenia. Concomitantly, there is a growing use of these agents used in the treatment of obsessive-compulsive disorder (OCD). Areas covered: This article provides a review of glutamate-modulating drugs used in the treatment of OCD. Specifically, the authors examine riluzole, N-acetylcysteine, d-cycloserine, glycine, ketamine, memantine and acamprosate as treatments. Furthermore, recent genetic epidemiology research findings are presented with a focus on the positional candidate genes SLC1A1 (a glutamate transporter), ADAR3 (an RNA-editing enzyme), RYR3 (a Ca(2+) channel), PBX1 (a homeobox transcription factor) and a GWAS candidate gene, DLGAP1 (a protein interacting with post-synaptic density). These genetic findings are submitted to a curated bioinformatics database to conform a biological network for discerning potential pharmacological targets. Expert opinion: In the genetically informed network, known genes and identified key connecting components, including DLG4 (a developmental gene), PSD-95 (a synaptic scaffolding protein) and PSEN1 (presenilin, a regulator of secretase), conform a group of potential pharmacological targets. These potential targets can be explored, in the future, to deliver new therapeutic approaches to OCD. There is also the need to develop a better understanding of neuroprotective mechanisms as a foundation for future OCD drug discovery.
    Expert Opinion on Drug Discovery 10/2013; DOI:10.1517/17460441.2013.845553 · 3.47 Impact Factor