Cited by 404Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchDementia and Cognitive Impairment Research

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The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidence

Danysz, Wojciech, Parsons, Chris G.·2003·International Journal of Geriatric Psychiatry

DOI 10.1002/gps.938

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Abstract

There is increasing evidence for the involvement of glutamate-mediated neurotoxicity in the pathogenesis of Alzheimer's disease (AD). We suggest that glutamate receptors of the N-methyl-D-aspartate (NMDA) type are overactivated in a tonic rather than a phasic manner in this disorder. This continuous mild activation may lead to neuronal damage and impairment of synaptic plasticity (learning). It is likely that under such conditions Mg(2+) ions, which block NMDA receptors under normal resting conditions, can no longer do so. We found that overactivation of NMDA receptors using a direct agonist or a decrease in Mg(2+) concentration produced deficits in synaptic plasticity (in vivo: passive avoidance test and/or in vitro: LTP in the CA1 region). In both cases, memantine-an uncompetitive NMDA receptor antagonists with features of an 'improved' Mg(2+) (voltage-dependency, kinetics, affinity)-attenuated this deficit. Synaptic plasticity was restored by therapeutically-relevant concentrations of memantine (1 microM). Moreover, doses leading to similar brain/serum levels provided neuroprotection in animal models relevant for neurodegeneration in AD such as neurotoxicity produced by inflammation in the NBM or beta-amyloid injection to the hippocampus. As such, if overactivation of NMDA receptors is present in AD, memantine would be expected to improve both symptoms (cognition) and to slow down disease progression because it takes over the physiological function of magnesium.

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Authors: Danysz, W., & Parsons, C. G.
Affiliations: Merz (Germany) (DE)
Corresponding author: Danysz, Wojciech
ORCID: Danysz, Wojciech
Parsons, Chris G.
Venue: International Journal of Geriatric Psychiatry
Publisher: Wiley
Published: 2003
Volume: 18
Issue: S1
Pages: S23-S32
ISSN: 0885-6230 (ISSN-L)
1099-1166
DOI: 10.1002/gps.938
OpenAlex: W2117396078
Cited by: 404
References: 49
Citations by year: 2026: 10 · 2025: 15 · 2024: 20 · 2023: 20 · 2022: 18 · 2021: 18 · 2020: 19 · 2019: 16 · 2018: 11 · 2017: 10 · 2016: 14 · 2015: 17 · 2014: 21 · 2013: 17 · 2012: 16
FWCI: 2.13
Type: journal article
Language: en
Open access: closed
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 4626 d)
Locations: International Journal of Geriatric Psychiatry (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: memantine, Alzheimer's disease, NMDA receptor antagonism, glutamate excitotoxicity, magnesium, synaptic plasticity, long-term potentiation, hippocampal CA1, neuroprotection, amyloid-beta, neuroinflammation, cognitive impairment
MeSH terms: Aged, Alzheimer Disease, Drug Evaluation, Preclinical, Humans, Memantine, Neuronal Plasticity, Receptors, N-Methyl-D-Aspartate, Excitatory Amino Acid Antagonists, Neuroprotective Agents

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The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidence

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