Abstract
Memantine, a partial antagonist of N-methyl-D-aspartate receptor (NMDAR), approved for moderate to severe Alzheimer’s disease (AD) treatment within the US and Europe under brand name Namenda (Forest), Axura and Akatinol (Merz), and Ebixa and Abixa (Lundbeck), may have potential in alleviating additional neurological conditions, such as vascular dementia (VD) and Parkinson’s disease (PD). In various animal models, memantine has been reported to be a neuroprotective agent that positively impacts both neurodegenerative and vascular processes. While excessive levels of glutamate result in neurotoxicity, in part through the over-activation of NMDARs, memantine—as a partial NMDAR antagonist, blocks the NMDA glutamate receptors to normalize the glutamatergic system and ameliorate cognitive and memory deficits. The key to memantine’s therapeutic action lies in its uncompetitive binding to the NMDAR through which low affinity and rapid off-rate kinetics of memantine at the level of the NMDAR-channel preserves the physiological function of the receptor, underpinning memantine’s tolerability and low adverse event profile. As the biochemical pathways evoked by NMDAR antagonism also play a role in PD and since no other drug is sufficiently effective to substitute for the first-line treatment of L-dopa despite its side effects, memantine may be useful in PD treatment with possibly fewer side effects. In spite of the relative modest nature of its adverse effects, memantine has been shown to provide only a moderate decrease in clinical deterioration in AD and VD, and hence efforts are being undertaken in the design of new and more potent memantine-based drugs to hopefully provide greater efficacy.
Keywords: Alzheimer’s disease, Parkinson’s disease, vascular dementia, memantine, NMDAR, amantadine, epigenetic, antagonists, amyloid precursor protein
Current Alzheimer Research
Title:N-Methyl D-Aspartate (NMDA) Receptor Antagonists and Memantine Treatment for Alzheimer’s Disease, Vascular Dementia and Parkinson’s Disease
Volume: 9 Issue: 6
Author(s): David Olivares, Varun K. Deshpande, Ying Shi, Debomoy K. Lahiri, Nigel H. Greig, Jack T. Rogers and Xudong Huang
Affiliation:
Keywords: Alzheimer’s disease, Parkinson’s disease, vascular dementia, memantine, NMDAR, amantadine, epigenetic, antagonists, amyloid precursor protein
Abstract: Memantine, a partial antagonist of N-methyl-D-aspartate receptor (NMDAR), approved for moderate to severe Alzheimer’s disease (AD) treatment within the US and Europe under brand name Namenda (Forest), Axura and Akatinol (Merz), and Ebixa and Abixa (Lundbeck), may have potential in alleviating additional neurological conditions, such as vascular dementia (VD) and Parkinson’s disease (PD). In various animal models, memantine has been reported to be a neuroprotective agent that positively impacts both neurodegenerative and vascular processes. While excessive levels of glutamate result in neurotoxicity, in part through the over-activation of NMDARs, memantine—as a partial NMDAR antagonist, blocks the NMDA glutamate receptors to normalize the glutamatergic system and ameliorate cognitive and memory deficits. The key to memantine’s therapeutic action lies in its uncompetitive binding to the NMDAR through which low affinity and rapid off-rate kinetics of memantine at the level of the NMDAR-channel preserves the physiological function of the receptor, underpinning memantine’s tolerability and low adverse event profile. As the biochemical pathways evoked by NMDAR antagonism also play a role in PD and since no other drug is sufficiently effective to substitute for the first-line treatment of L-dopa despite its side effects, memantine may be useful in PD treatment with possibly fewer side effects. In spite of the relative modest nature of its adverse effects, memantine has been shown to provide only a moderate decrease in clinical deterioration in AD and VD, and hence efforts are being undertaken in the design of new and more potent memantine-based drugs to hopefully provide greater efficacy.
Export Options
About this article
Cite this article as:
Olivares David, K. Deshpande Varun, Shi Ying, K. Lahiri Debomoy, H. Greig Nigel, T. Rogers Jack and Huang Xudong, N-Methyl D-Aspartate (NMDA) Receptor Antagonists and Memantine Treatment for Alzheimer’s Disease, Vascular Dementia and Parkinson’s Disease, Current Alzheimer Research 2012; 9 (6) . https://dx.doi.org/10.2174/156720512801322564
DOI https://dx.doi.org/10.2174/156720512801322564 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
An Overview of the Pharmacological Properties and Potential Applications of Natural Monoterpenes
Mini-Reviews in Medicinal Chemistry Management of the Low Cardiac Output Syndrome Following Surgery for Congenital Heart Disease
Current Cardiology Reviews CD20-based Immunotherapy of B-cell Derived Hematologic Malignancies
Current Cancer Drug Targets Impaired Cerebral Autoregulation and Vasomotor Reactivity in Sporadic Alzheimer’s Disease
Current Alzheimer Research Development of Small Molecule Non-peptide Formyl Peptide Receptor (FPR) Ligands and Molecular Modeling of Their Recognition
Current Medicinal Chemistry Rediscovering Tocophersolan: A Renaissance for Nano-Based Drug Delivery and Nanotheranostic Applications
Current Drug Targets Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease
Current Pharmaceutical Design The Nutritional Characteristics of the Hypotensive WASHOKU-modified DASH Diet: A Sub-analysis of the DASH-JUMP Study
Current Hypertension Reviews Common and Less Common Peripheral Nerve Disorders Associated with Diabetes
Current Diabetes Reviews The Risk of Adverse Drug Reactions in Older Patients: Beyond Drug Metabolism
Current Drug Metabolism Prevention and Management of Ovarian Hyperstimulation Syndrome
Current Women`s Health Reviews Antioxidant Properties and Medicinal Uses of Some Crataegus Spp. (Hawthorn) Including <i>C. meyeri</i> and <i>C. pontica</i>
Current Nutrition & Food Science Current Advances in L-DOPA and DOPA-Peptidomimetics: Chemistry, Applications and Biological Activity
Current Medicinal Chemistry ARC - Augmented Renal Clearance
Current Pharmaceutical Biotechnology Safety and Efficacy of Aliskiren in the Treatment of Hypertension and Associated Clinical Conditions
Current Drug Safety The ONTARGET Trial Programme: Facts and Lessons
Current Hypertension Reviews Initiating Structural Studies Of Lys49-Pla2 Homologues Complexed With An Anionic Detergent, A Fatty Acid And A Natural Lipid
Protein & Peptide Letters Tityus serrulatus Scorpion Venom and Toxins: An Overview
Protein & Peptide Letters The Future of Angiotensin II Inhibition in Cardiovascular Medicine
Current Drug Targets - Cardiovascular & Hematological Disorders Recent Insights into COVID-19 in Children and Clinical Recommendations
Current Pediatric Reviews