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Drugs of Today (Barcelona, Spain : 1998) Aug 2004Memantine (Axura, Merz Pharmaceuticals GmbH; Ebixa, H. Lundbeck A/S, Namenda, Forest Laboratories, Inc.) is an uncompetitive N-methyl-D-aspartate (NMDA) receptor... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Memantine (Axura, Merz Pharmaceuticals GmbH; Ebixa, H. Lundbeck A/S, Namenda, Forest Laboratories, Inc.) is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist with low to moderate affinity for the (+)MK-801 binding site. It is characterized as a voltage-sensitive open-channel NMDA receptor blocker that antagonizes NMDA receptor-mediated inward currents in vitro with an IC50 of 1-3 microM. In animal models, memantine displays both neuroprotective (antiexcitotoxic) and cognition-enhancing properties at therapeutically relevant concentrations. The strong voltage dependency and rapid blocking/unblocking kinetics of memantine are thought to be the basis for its excellent clinical tolerability. Recently completed clinical studies demonstrate positive effects of memantine in Alzheimer's disease both as a monotherapy and in patients receiving continuous donepezil treatment. Memantine treatment also has demonstrated significant improvement of cognitive performance in patients suffering from vascular dementia. Furthermore, the safety and tolerability of memantine in clinical trials has been excellent, with the incidence of premature withdrawals due to adverse events no greater than placebo and overall low frequencies of total adverse events. In 2002, memantine was approved by the European Medicines Agency (EMEA) for the treatment of moderately severe to severe Alzheimer's disease. More recently, memantine was approved in the US for the treatment of moderate to severe Alzheimer's disease (October 2003). Here, we review the most recent pharmacological and clinical data in dementia patients that has emerged from the systematic evaluation of memantine.
Topics: Alzheimer Disease; Animals; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cross-Over Studies; Double-Blind Method; Humans; Memantine; Molecular Structure
PubMed: 15510240
DOI: No ID Found -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2017Memantine is the first clinically available glutamate antagonist, with an antagonist action at the N-methyl-D-aspartate receptors in the brain, for correction of... (Review)
Review
Memantine is the first clinically available glutamate antagonist, with an antagonist action at the N-methyl-D-aspartate receptors in the brain, for correction of cognitive and behavioral functions in neurodegenerative disorders. Glutamate mediated excitotoxic neuronal damage has been implicated in Alzheimer's disease (AD) and other parkinsonism-related dementias and, therefore, memantine represents a novel mode of action to counteract the glutamate-mediated excitotoxicity. In moderate to severe AD, 20 mg of memantine shows a positive effect on cognition, mood, behavior and the ability to perform activities of daily living. Long-term studies show good tolerability of memantine with an acceptable side-effect profile. In recent years, there have been a proliferation of a number of companies producing generic memantine with different trade names. In Russia, the first memantine generic drug noojerone was approved in 2010 and its use has since been supported by a growing evidence base of efficacy in real-life clinical practice. Postmarketing studies show that noojerone provides long-term and effective therapy in patients with moderate and severe Alzheimer's dementia. This observation is supported by the clinically significant therapeutic effect of noojerone on cognitive and daily functioning, behavioral and psychotic symptoms of dementia and a reduction of the burden on caregivers. This generic version of memantine is affordable and, therefore, reduces financial burden on patients and improves compliance with treatment.
Topics: Activities of Daily Living; Alzheimer Disease; Antiparkinson Agents; Brain; Drugs, Generic; Excitatory Amino Acid Antagonists; Glutamic Acid; Humans; Memantine; Neurons; Receptors, N-Methyl-D-Aspartate; Russia
PubMed: 29171502
DOI: 10.17116/jnevro2017117101136-143 -
Bioengineered Mar 2022Oxaliplatin is an effective chemotherapeutic agent for the treatment of malignant tumors. However, severe oxaliplatin-induced neurotoxicity has been well documented....
Oxaliplatin is an effective chemotherapeutic agent for the treatment of malignant tumors. However, severe oxaliplatin-induced neurotoxicity has been well documented. Memantine is a drug for the management of Alzheimer's Disease (AD) due to its promising neuroprotective properties. We hypothesize that Memantine possesses a beneficial role against chemotherapy-induced neuronal damages. In this study, we established an oxaliplatin-induced neurotoxicity assay model in human SHSY-5Y neuronal cells and investigated the protective effect of Memantine. We showed that Memantine treatment ameliorated oxaliplatin-elevated intracellular production of reactive oxygen species (ROS), lipid product malondialdehyde (MDA), and NOX-2 expression. Memantine alleviated impairment of the mitochondrial membrane potential and ATP production by oxaliplatin. As a result, Memantine showed a protective role against oxaliplatin-induced cytotoxicity. Moreover, the terminal deoxynucleotidyl Transferase-mediated dUTP nick end labeling (TUNEL) apoptosis assay revealed that Memantine protected oxaliplatin-induced apoptosis through mitigating the ratio of Bax/Bcl-2 and Caspase-3 cleavage. We concluded Memantine ameliorated the neurotoxicity of oxaliplatin in a mitochondrial-dependent pathway.
Topics: Apoptosis; Humans; Memantine; Membrane Potential, Mitochondrial; Mitochondria; Oxaliplatin; Oxidative Stress; Reactive Oxygen Species
PubMed: 35235756
DOI: 10.1080/21655979.2022.2026553 -
Expert Opinion on Pharmacotherapy Sep 2014In people with moderate-to-severe dementia in Alzheimer's disease (AD) memantine provides some clinical benefits. It is commonly administered twice daily at a maximum...
INTRODUCTION
In people with moderate-to-severe dementia in Alzheimer's disease (AD) memantine provides some clinical benefits. It is commonly administered twice daily at a maximum dose of 20 mg. To improve medication adherence, convenience of use and to enable a higher daily dose, a 28 mg, extended-release formulation of memantine has been developed.
AREAS COVERED
We review the results of a Phase III randomized and controlled trial of memantine extended release as an add-on treatment and compared the findings with a similarly designed previous trial evaluating the immediate release (IR) form.
EXPERT OPINION
Memantine extended release produced minor benefits on cognitive ability, including verbal fluency, behavioral problems and global clinical assessment. There was no difference between the treatment groups on activities of daily living. The observed effects were not larger than those of the IR formulation tested in a similar setting. The lack of impact on activities of daily living suggests that the small improvements in cognition and behavior did not translate into clinically important changes. In conclusion, there is no convincing evidence that the novel once-daily formulation of memantine represents a significant progress in the clinical management of AD that would justify additional treatment costs.
Topics: Activities of Daily Living; Alzheimer Disease; Cognition Disorders; Excitatory Amino Acid Antagonists; Humans; Medication Adherence; Memantine; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate
PubMed: 25085661
DOI: 10.1517/14656566.2014.945907 -
CNS Drugs Nov 2015A once-daily, fixed-dose combination of memantine extended-release (ER)/donepezil 28/10 mg (Namzaric™) is available in the USA for patients with moderate to severe... (Review)
Review
A once-daily, fixed-dose combination of memantine extended-release (ER)/donepezil 28/10 mg (Namzaric™) is available in the USA for patients with moderate to severe Alzheimer's disease (AD) on stable memantine and donepezil therapy. The fixed-dose formulation is bioequivalent to coadministration of the individual drugs. In a 24-week, phase III trial in patients with moderate to severe AD, addition of memantine ER 28 mg once daily to stable cholinesterase inhibitor (ChEI) therapy was more effective than add-on placebo on measures of cognition, global clinical status, dementia behaviour and semantic processing ability, although between-group differences on a measure of daily function did not significantly differ. In subgroup analyses in donepezil-treated patients, add-on memantine ER was more effective than add-on placebo on measures of cognition, dementia behaviour and semantic processing, although there were no significant between-group differences on measures of global clinical status and daily function. Memantine ER plus ChEI combination therapy was generally well tolerated in the phase III trial, with diarrhoea, dizziness and influenza occurring at least twice as often with add-on memantine ER as add-on placebo in donepezil-treated patients. Thus, memantine ER plus donepezil combination therapy is an effective and well tolerated treatment option for patients with moderate to severe AD. The fixed-dose combination is potentially more convenient than coadministration of the individual agents.
Topics: Alzheimer Disease; Clinical Trials, Phase III as Topic; Drug Combinations; Humans; Memantine; Nootropic Agents; Piperidines
PubMed: 26519339
DOI: 10.1007/s40263-015-0287-2 -
Annals of Clinical Psychiatry :... May 2020
Topics: Adolescent; Dopamine Agents; Female; Humans; Memantine; Off-Label Use; Trichotillomania
PubMed: 32343286
DOI: No ID Found -
The Lancet. Neurology Aug 2003The use of cholinesterase inhibitors to correct the cholinergic deficit in patients with mild to moderate Alzheimer's disease (AD) is well established. However, the... (Review)
Review
BACKGROUND
The use of cholinesterase inhibitors to correct the cholinergic deficit in patients with mild to moderate Alzheimer's disease (AD) is well established. However, the treatment is only effective in about half of the patients for whom it is prescribed. Vascular dementia may respond, at least to some extent, to these drugs (T Erkinjuntti and colleagues, Lancet 2002; 359: 1283-90). In 2002, the Committee of Proprietary Medicinal Products recommended that memantine-a drug that acts on the glutamatergic system rather than the cholinergic system-be approved by the European Commission for the treatment of moderately severe to severe AD. Clinical trials have shown some effectiveness of memantine in the treatment of vascular dementia, although it has not been approved for use in this disorder.
RECENT DEVELOPMENTS
The results of a study of the effects of memantine on moderate to severe AD have recently been published (B Reisberg and colleagues, N Engl J Med 2003; 348: 1333-41). Reisberg and colleagues treated their patients for 28 weeks, assessed several outcome variables, and found that memantine reduced clinical deterioration without significant adverse effects. This study is important as memantine is the only treatment licensed for patients with more advanced AD. WHERE NEXT? Several questions about the use of memantine as a treatment for AD remain to be answered. How beneficial is memantine treatment in routine clinical practice compared with clinical trials? What is the best way to assess treatment effects? How long do the beneficial effects last? Does memantine have neuroprotective, rather than just symptomatic, effects? In addition, we need to know when to switch from cholinesterase inhibitors to memantine or when to co-prescribe memantine with cholinesterase inhibitors. The efficacy of memantine in vascular dementia also requires further investigation.
Topics: Animals; Dementia; Humans; Memantine
PubMed: 12878438
DOI: 10.1016/s1474-4422(03)00486-1 -
Molecules (Basel, Switzerland) Sep 2020Memantine (3,5-dimethyladamantan-1-amine) is an orally active, noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist approved for treatment of... (Review)
Review
Memantine (3,5-dimethyladamantan-1-amine) is an orally active, noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist approved for treatment of moderate-to-severe Alzheimer's disease (AD), a neurodegenerative condition characterized by a progressive cognitive decline. Unfortunately, memantine as well as the other class of drugs licensed for AD treatment acting as acetylcholinesterase inhibitors (AChEIs), provide only symptomatic relief. Thus, the urgent need in AD drug development is for disease-modifying therapies that may require approaching targets from more than one path at once or multiple targets simultaneously. Indeed, increasing evidence suggests that the modulation of a single neurotransmitter system represents a reductive approach to face the complexity of AD. Memantine is viewed as a privileged NMDAR-directed structure, and therefore, represents the driving motif in the design of a variety of multi-target directed ligands (MTDLs). In this review, we present selected examples of small molecules recently designed as MTDLs to contrast AD, by combining in a single entity the amantadine core of memantine with the pharmacophoric features of known neuroprotectants, such as antioxidant agents, AChEIs and Aβ-aggregation inhibitors.
Topics: Alzheimer Disease; Animals; Antioxidants; Cholinesterase Inhibitors; Drug Design; Humans; Memantine; Models, Molecular
PubMed: 32887400
DOI: 10.3390/molecules25174005 -
International Journal of Pharmaceutical... 2023Memantine hydrochloride is commonly prescribed for Alzheimer's disease and vascular dementia. However, the drug is only available in tablet form, a dosage form which...
Memantine hydrochloride is commonly prescribed for Alzheimer's disease and vascular dementia. However, the drug is only available in tablet form, a dosage form which is difficult for geriatrics to swallow. This problem is especially difficult for those patients diagnosed with Alzheimer's. This study was therefore aimed to develop and characterize an oral disintegrating film containing memantine hydrochloride using different types and concentrations of polymers. Using the solvent casting method, twelve formulations were developed, which involved manipulations on the type and concentration of the polymer. Afterwards, six formulations were selected to undergo characterization tests. These tests evaluated the films' tensile strength, Young's Modulus, percent elongation, folding endurance, disintegration and dissolution time, content uniformity, moisture loss, and moisture uptake. Polymers such as polyvinyl alcohol, hydroxypropyl methylcellulose, polyvinyl pyrrolidone, and pullulan gum were respectively incorporated at different concentrations. The study found that only hydroxypropyl methylcellulose and polyvinyl alcohol formulations developed into acceptable oral disintegrating films. Formulation E (hydroxypropyl methylcellulose 50-mg/film), which exhibited optimal mechanical strength, fast disintegration and dissolution, and excellent content uniformity, was identified as the best formula. Although polyvinyl alcohol showed higher mechanical strength, hydroxypropyl methylcellulose films were better at fulfilling the optimal characteristics of an oral disintegrating film. The study showed that the mechanical strength increased proportionally to the polymer concentration in the polyvinyl alcohol film. However, for the hydroxypropyl methylcellulose film, the mechanical strength increased only when hydroxypropyl methylcellulose's concentration was increased from a 40-mg/film to a 50-mg/film but decreased with a 60-mg/film. To summarize, orally disintegrating films containing memantine hydrochloride was developed, characterized, and reasoned to have high potential to be marketed and to increase medication compliance among geriatrics suffering from Alzheimer's disease.
Topics: Humans; Aged; Chemistry, Pharmaceutical; Memantine; Polyvinyl Alcohol; Alzheimer Disease; Administration, Oral; Hypromellose Derivatives; Solubility; Polymers; Drug Compounding
PubMed: 38100669
DOI: No ID Found -
Journal of Affective Disorders Jun 2022To date, there is limited evidence on the antidepressant effects of memantine in patients with major mental diseases. We conducted a systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Review
The efficacy and tolerability of memantine for depressive symptoms in major mental diseases: A systematic review and updated meta-analysis of double-blind randomized controlled trials.
OBJECTIVE
To date, there is limited evidence on the antidepressant effects of memantine in patients with major mental diseases. We conducted a systematic review and meta-analysis to assess the efficacy of memantine in such populations.
METHODS
A literature search was performed for randomized controlled trials (RCTs) from the date of their inception until September 28, 2021, using PubMed, Medline, Embase, and the Cochrane Library. Changes in depression scores were the primary outcome. The response rate and remission rate to the treatment were secondary outcomes. We also assessed the dropout rate for tolerance.
RESULTS
Eleven double-blind RCTs were included with 899 participants. Memantine significantly reduced depressive symptom scores compared with the control group (k = 11, n = 899, Hedges' g = -0.17, 95% confidence interval [CI] = -0.30 to -0.04, p = 0.009) with a small effect size. For secondary outcomes, memantine did not show a significant effect on response rate nor remission rate. In the subgroup analysis, memantine significantly reduced depressive symptom scores in patients with mood disorders (k = 8, n = 673, Hedges' g = -0.17, 95% CI = -0.32 to -0.01, p = 0.035) with a small effect size, but not in patients with schizophrenia.
CONCLUSION
The present meta-analysis indicates that memantine effectively alleviates depressive symptoms in patients with mood disorders with a small effect size. Furthermore, memantine is well-tolerated and acceptable.
Topics: Antidepressive Agents; Depression; Humans; Memantine; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 35331821
DOI: 10.1016/j.jad.2022.03.047