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Expert Opinion on Investigational Drugs Jun 2000Memantine, a non-competitive NMDA antagonist, has been approved for use in the treatment of dementia in Germany for over ten years. The rationale for use is... (Review)
Review
Memantine, a non-competitive NMDA antagonist, has been approved for use in the treatment of dementia in Germany for over ten years. The rationale for use is excitotoxicity as a pathomechanism of neurodegenerative disorders. Memantine acts as a neuroprotective agent against this pathomechanism, which is also implicated in vascular dementia. HIV-1 proteins Tat and gp120 have been implicated in the pathogenesis of dementia associated with HIV infection and the neurotoxicity caused by HIV-1 proteins can be blocked completely by memantine. Memantine has been investigated extensively in animal studies and following this, its efficacy and safety has been established and confirmed by clinical experience in humans. It exhibits none of the undesirable effects associated with competitive NMDA antagonists such as dizocilpine. The efficacy of memantine in a variety of dementias has been shown in clinical trials. Memantine is considered to be a promising neuroprotective drug for the treatment of dementias, particularly Alzheimer's disease for which there is no neuroprotective therapy available currently. It can be combined with acetylcholinesterase inhibitors which are the mainstay of current symptomatic treatment of Alzheimer's disease. Memantine has a therapeutic potential in numerous CNS disorders besides dementias which include stroke, CNS trauma, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), epilepsy, drug dependence and chronic pain. If memantine is approved by the FDA for some of these indications by the year 2005, it can become a blockbuster drug by crossing the US$1 billion mark in annual sales.
Topics: Alzheimer Disease; Animals; Dementia; Humans; Memantine; Neuroprotective Agents
PubMed: 11060751
DOI: 10.1517/13543784.9.6.1397 -
CNS Drugs Oct 2009Memantine is an uncompetitive, moderate-affinity NMDA receptor antagonist that is indicated for the treatment of moderate to severe Alzheimer's disease. In well designed... (Review)
Review
Memantine is an uncompetitive, moderate-affinity NMDA receptor antagonist that is indicated for the treatment of moderate to severe Alzheimer's disease. In well designed trials in patients with moderate to severe Alzheimer's disease, oral memantine monotherapy improved outcomes in the area of functional ability more than placebo in one trial, but in a second trial, treatment differences did not reach significance. Memantine has a distinct mode of action compared with that of acetylcholinesterase (AChE) inhibitors, and in a well designed study, combination therapy with memantine plus donepezil improved outcomes more than donepezil plus placebo in all four domains (function, cognition, behaviour and global change). Memantine is generally well tolerated, with adverse events occurring with a similar incidence to that reported with placebo. In modelled cost-effectiveness analyses, memantine was dominant to no therapy in regard to cost per quality-adjusted life-year (QALY) gained, and the combination of memantine plus donepezil was dominant to donepezil therapy alone in regard to QALYs gained when treatment periods exceeded 1 year in patients with moderate to severe disease. Thus, in the management of patients with moderate to severe Alzheimer's disease, memantine provides an effective treatment option. To date, clinical trial support is greater for memantine use in combination with an AChE inhibitor, while more data are needed to confirm its efficacy as monotherapy.
Topics: Alzheimer Disease; Clinical Trials as Topic; Humans; Memantine; Severity of Illness Index
PubMed: 19739697
DOI: 10.2165/11201020-000000000-00000 -
The American Journal of Geriatric... Dec 2004Until recently, acetylcholinesterase inhibitors were the only approved agents for the treatment of Alzheimer's disease (AD). These medications have also been used in the... (Review)
Review
BACKGROUND
Until recently, acetylcholinesterase inhibitors were the only approved agents for the treatment of Alzheimer's disease (AD). These medications have also been used in the treatment of vascular dementia (VD). Memantine, the first N-methyl-D-aspartate (NMDA)-receptor antagonist to be well tolerated, has been approved for the treatment of moderate to severe AD.
OBJECTIVE
The aim of this study was to review the current literature on the efficacy and tolerability of memantine in the treatment of AD and VD.
METHODS
A MEDLINE search of the English-language literature from January 1970 to March 2004 was conducted to identify randomized, double-blind, placebo-controlled, parallel-group trials in which memantine was administered to patients with VD or AD. The search terms were memantine, NMDA inhibitor, and NMDA antagonist.
RESULTS
Excessive glutamate, the brain's major excitatory neurotransmitter, can cause excitotoxicity by allowing too much calcium to enter neuronal cells. Moderate-affinity NMDA-receptor antagonists such as memantine block pathologic activity of glutamate while allowing physiologic activity. Use of memantine has been associated with significant improvements in measures of cognition, function, and behavior in both VD and AD. Adverse events associated with memantine have been comparable to those with placebo, with the exception of an increased incidence of dizziness, constipation, cataracts, nausea, dyspnea, confusion, headache, and urinary incontinence.
CONCLUSIONS
Memantine seems to be promising and well tolerated in the treatment of moderate to severe VD or AD, either as monotherapy or in combination with donepezil. It appears to be particularly effective in improving cognitive, functional, and global outcomes in moderate to severe AD and in improving cognitive end points in mild to moderate VD. More research is needed on important clinical questions, including whether memantine can prolong patients' ability to provide self-care and delay institutional placement.
Topics: Aged; Alzheimer Disease; Clinical Trials as Topic; Dementia, Vascular; Humans; Memantine; Receptors, N-Methyl-D-Aspartate
PubMed: 15903287
DOI: 10.1016/j.amjopharm.2004.12.006 -
Magnetic Resonance in Chemistry : MRC Aug 2016The use of quantitative nuclear magnetic resonance spectrometry for the determination of non-UV active memantine hydrochloride with relative simplicity and precision has...
The use of quantitative nuclear magnetic resonance spectrometry for the determination of non-UV active memantine hydrochloride with relative simplicity and precision has been demonstrated in this study. The method was developed on a 500 MHz NMR instrument and was applied to determination of the drug in a tablet formulation. The analysis was performed by taking caffeine as an internal standard and D2 O as the NMR solvent. The signal of methyl protons of memantine hydrochloride appeared at 0.75 ppm (singlet) relative to the signal of caffeine (internal standard) at 3.13 ppm (singlet). The method was found to be linear (r(2) = 0.9989) in the drug concentration range of 0.025 to 0.80 mg/ml. The maximum relative standard deviation for accuracy and precision was <2. The limits of detection and quantification were 0.04 and 0.11 mg/ml, respectively. The robustness of the method was revealed by changing nine different parameters. The deviation for each parameter was also within the acceptable limits. The study highlighted possibility of direct determination of memantine hydrochloride in pure form and in its marketed tablet formulation by the use of quantitative NMR, without the need of derivatization, as is the requirement in HPLC studies. Copyright © 2016 John Wiley & Sons, Ltd.
Topics: Algorithms; Antiparkinson Agents; Caffeine; Drug Compounding; Limit of Detection; Magnetic Resonance Spectroscopy; Memantine; Reference Standards; Reproducibility of Results; Tablets
PubMed: 26923624
DOI: 10.1002/mrc.4421 -
Drugs May 2015Memantine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that is a well-established treatment option for moderate to severe dementia of the... (Review)
Review
Memantine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that is a well-established treatment option for moderate to severe dementia of the Alzheimer's type, either alone or in combination with cholinesterase inhibitors. The immediate-release (IR) formulations of memantine (tablets and oral solution) have been available in numerous countries, including the USA, for more than a decade and are administered orally twice daily at a maximum recommended total daily dosage of 20 mg/day. The memantine extended-release (ER) (Namenda XR(®)) 28 mg once-daily capsule formulation was approved in the USA in 2010 and became available more recently. The potential advantages of memantine ER over the IR formulation include a more convenient dosage regimen and lower pill burden that may improve adherence to therapy; also, memantine ER capsules may be opened and the contents sprinkled on applesauce for patients who have difficulty swallowing. Memantine ER provides a higher total daily dosage than the recommended memantine IR regimen and pharmacokinetic data indicate greater exposure with the ER formulation, but the clinical implications of this are unclear, as the two formulations have not been assessed in a comparative clinical trial. The efficacy of memantine ER 28 mg once daily was demonstrated in a large, multinational, phase III trial, which showed that the addition of memantine ER to ongoing oral cholinesterase inhibitors improved key outcomes compared with cholinesterase inhibitor monotherapy, including measures of cognition and global status, which were the co-primary endpoints of the study. The most common adverse events were headache, diarrhoea and dizziness.
Topics: Alzheimer Disease; Delayed-Action Preparations; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Humans; Memantine; Receptors, N-Methyl-D-Aspartate
PubMed: 25899711
DOI: 10.1007/s40265-015-0400-3 -
Journal of Alzheimer's Disease : JAD 2013Memantine is approved as a treatment for moderate to severe Alzheimer's disease (AD). However, recent studies report that memantine is harmful for AD patients in several... (Review)
Review
BACKGROUND/OBJECTIVE
Memantine is approved as a treatment for moderate to severe Alzheimer's disease (AD). However, recent studies report that memantine is harmful for AD patients in several ways. This paper will systematically review all the available studies to provide an update regarding memantine as a treatment for AD.
METHOD
Two authors queried nine databases containing literature published prior to September 15, 2012 and determined eligible studies based on the inclusion criteria. We used Review Manager to pool similar data. The Cochrane Handbook was used to assess the bias of the included studies. The chi-squared test, sensitivity analysis, Egger's test, and funnel plots were used to determine the heterogeneity and report bias, respectively.
RESULT
We obtained 889 studies and determined that 12 of those studies met the inclusion criteria. The pooled analysis showed that memantine had significant benefits for AD patients in terms of cognition and the clinician's global impression. There were no significant benefits for AD patients in terms of mental state or activities of daily life. The results on brain volume and metabolism were controversial in two of the studies. Memantine did not significantly affect discontinuation caused by serious adverse events but did increase the risk for somnolence, weight gain, confusion, hypertension, nervous system disorders, and falling.
CONCLUSION
Memantine is beneficial for AD patients with regards to cognition and clinician's global impression but increases the risk for somnolence, weight gain, confusion, hypertension, nervous system disorders, and falling.
Topics: Alzheimer Disease; Cognition; Excitatory Amino Acid Antagonists; Humans; Memantine; Treatment Outcome
PubMed: 23635410
DOI: 10.3233/JAD-130395 -
Molecular Pharmaceutics May 2022Alzheimer's disease is a chronic disease, and the long-term treatment of chronic diseases has always been a concern. Memantine (Mem) is approved by the US Food and Drug...
Alzheimer's disease is a chronic disease, and the long-term treatment of chronic diseases has always been a concern. Memantine (Mem) is approved by the US Food and Drug Administration for the treatment of moderate to severe Alzheimer's disease. In this study, reactions of memantine (Mem) with pamoic acid (Pam) were carried out to form insoluble salts (Mem-Pam). Four polymorphic forms (Forms I-IV) of Mem-Pam were successfully obtained through polymorphic screening, which were systematically characterized by X-ray powder diffraction (PXRD), thermal analysis (TGA and DSC), single-crystal X-ray diffraction (SXRD), and solid-state fluorescence. Compared with the hydrochloride form, the dissolution and release rates of these four forms are lower. The presence of pamoic acid reduces the release rate of memantine and makes it possible to achieve a sustained release of the drug. Interestingly, because of the presence of memantine, each polymorphic solid crystal of Mem-Pam has unique fluorescence emission. Therefore, memantine and pamoic acid have a synergistic effect on the fluorescence performance and can be expected to be used for real-time monitoring in continuous and controlled release drug delivery systems. In addition, the polymorphic solid crystals also exhibit reversible mechanochromic luminescence under the fumigation of acetonitrile vapor, which has a guiding role in the fluorescence design and synthesis of Pam substances and is expected to be used for information security, visual inspection of organic substances, etc.
Topics: Alzheimer Disease; Humans; Memantine; Powders; Sodium Chloride; X-Ray Diffraction
PubMed: 35230851
DOI: 10.1021/acs.molpharmaceut.1c00931 -
CNS Drugs Aug 2012Memantine, a non-competitive NMDA receptor antagonist approved for Alzheimer's disease with a good safety profile, is increasingly being studied in a variety of... (Review)
Review
Memantine, a non-competitive NMDA receptor antagonist approved for Alzheimer's disease with a good safety profile, is increasingly being studied in a variety of non-dementia psychiatric disorders. We aimed to critically review relevant literature on the use of the drug in such disorders. We performed a PubMed search of the effects of memantine in animal models of psychiatric disorders and its effects in human studies of specific psychiatric disorders. The bulk of the data relates to the effects of memantine in major depressive disorder and schizophrenia, although more recent studies have provided data on the use of the drug in bipolar disorder as an add-on. Despite interesting preclinical data, results in major depression are not encouraging. Animal studies investigating the possible usefulness of memantine in schizophrenia are controversial; however, interesting findings were obtained in open studies of schizophrenia, but negative placebo-controlled, double-blind studies cast doubt on their validity. The effects of memantine in anxiety disorders have been poorly investigated, but data indicate that the use of the drug in obsessive-compulsive disorder and post-traumatic stress disorder holds promise, while findings relating to generalized anxiety disorder are rather disappointing. Results in eating disorders, catatonia, impulse control disorders (pathological gambling), substance and alcohol abuse/dependence, and attention-deficit hyperactivity disorder are inconclusive. In most psychiatric non-Alzheimer's disease conditions, the clinical data fail to support the usefulness of memantine as monotherapy or add-on treatment However, recent preclinical and clinical findings suggest that add-on memantine may show antimanic and mood-stabilizing effects in treatment-resistant bipolar disorder.
Topics: Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Excitatory Amino Acid Antagonists; Humans; Memantine; Mental Disorders; Treatment Outcome
PubMed: 22784018
DOI: 10.2165/11634390-000000000-00000 -
European Journal of Pharmacology May 2018A developing body of evidence indicates that disturbed glutamate neurotransmission especially through N-methyl-d-aspartate (NMDA) is central to the pathophysiology of... (Review)
Review
A developing body of evidence indicates that disturbed glutamate neurotransmission especially through N-methyl-d-aspartate (NMDA) is central to the pathophysiology of major depressive disorder (MDD) and NMDA receptor antagonists have shown therapeutic potential in the MDD treatment. Memantine is an uncompetitive NMDA receptor antagonist, approved for treatment of Alzheimer's disease (AD) that in contrast to other NMDA receptor antagonists at therapeutic doses does not induce highly undesirable side effects. Neuroprotective properties and well tolerability of memantine have been attributed to its unique pharmacological features such as moderate affinity, rapid blocking kinetics and strongly voltage-dependency. In this review we summarized clinical trial evidence of antidepressant effectiveness of memantine and its mechanisms of action. Available data indicate contradictory findings relating to clinical efficacy suggesting further research is necessary in determining as to whether memantine will eventually be an advantageous therapy for MDD. Preclinical data proposed various neurobiological mechanisms underlying antidepressant-like properties of memantine that are responsible for synaptic plasticity and cell survival.
Topics: Animals; Behavior, Animal; Clinical Trials as Topic; Depressive Disorder, Major; Humans; Memantine
PubMed: 29551658
DOI: 10.1016/j.ejphar.2018.03.023 -
Drugs & Aging Jan 2013In the EU, once-daily memantine 20 mg (Axura(®), Ebixa(®)) is an option for the management of patients with moderate to severe Alzheimer's disease (AD). In pooled... (Review)
Review
In the EU, once-daily memantine 20 mg (Axura(®), Ebixa(®)) is an option for the management of patients with moderate to severe Alzheimer's disease (AD). In pooled clinical trials and studies in the clinical practice setting, memantine 20 mg/day improved cognition, functional ability and behavioural symptoms in this patient population. The beneficial effects of memantine are associated with delays in the need for full-time care, which were predicted to result in cost savings relative to standard care in recent cost-utility analyses in patients with moderate to severe AD conducted in EU countries. Memantine is well tolerated, with an adverse event profile that is similar to that with placebo.
Topics: Alzheimer Disease; Cost-Benefit Analysis; Drug Administration Schedule; European Union; Humans; Memantine
PubMed: 23229767
DOI: 10.1007/s40266-012-0041-0