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Dementia and Geriatric Cognitive... 2009Memantine is a moderate-affinity, uncompetitive antagonist of N-methyl-D-aspartate receptors, approved for the treatment of moderate to severe Alzheimer's disease (AD).... (Review)
Review
Memantine is a moderate-affinity, uncompetitive antagonist of N-methyl-D-aspartate receptors, approved for the treatment of moderate to severe Alzheimer's disease (AD). Available data suggest that, in addition to its benefits on cognition, function, and global status, memantine treatment may also help alleviate behavioral symptoms. This article provides an overview of the prevalence, assessment, and treatment of behavioral disturbances in AD, and summarizes current knowledge regarding the effects of memantine on the behavior of community-dwelling patients. We searched EMBASE and PubMed (January 1992 to October 2008) for reports on memantine trials that involved outpatients with moderate to severe AD. All previously unpublished data were obtained from Forest Laboratories, Inc. Behavioral outcomes were assessed in three completed, double-blind, placebo-controlled trials.Overall, patients who received memantine performed better on behavioral measures than those treated with placebo. Post-hoc analyses suggest that memantine treatment was associated with a reduced severity or emergence of specific symptoms, particularly agitation and aggression. Prospective, well-designed trials are warranted to evaluate the efficacy of memantine in patients with significant behavioral symptoms.
Topics: Aged; Alzheimer Disease; Behavior; Excitatory Amino Acid Antagonists; Female; Humans; Male; Memantine; Neuropsychological Tests; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 19194105
DOI: 10.1159/000200013 -
Brain and Nerve = Shinkei Kenkyu No... May 2023Alzheimer's disease (AD) treatment includes both non-pharmacological and pharmacological approaches. Current pharmacological approaches include symptomatic and... (Review)
Review
Alzheimer's disease (AD) treatment includes both non-pharmacological and pharmacological approaches. Current pharmacological approaches include symptomatic and disease-modifying therapies (DMTs). In Japan, DMTs have not yet been approved for treating AD; however, four drugs are currently available for symptomatic therapies, including cholinesterase inhibitors (ChEIs) such as donepezil for mild-to-severe dementia, galantamine and rivastigmine for mild-to-moderate dementia, and memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, for moderate-to-severe dementia. In this review, we describe the use of four symptomatic anti-AD drugs in clinical practice for AD.
Topics: Humans; Cholinesterase Inhibitors; Alzheimer Disease; Donepezil; Rivastigmine; Galantamine; Memantine; Receptors, N-Methyl-D-Aspartate
PubMed: 37194514
DOI: 10.11477/mf.1416202360 -
Turkish Journal of Medical Sciences Jun 2022Cancer cells express higher levels of N-methyl-d-aspartate (NMDA) receptor. In this study, we aimed to use memantine as a potential blocker to inhibit the action of the...
BACKGROUND
Cancer cells express higher levels of N-methyl-d-aspartate (NMDA) receptor. In this study, we aimed to use memantine as a potential blocker to inhibit the action of the NMDA receptor in cancer cells in vivo in order to investigate the potential chemopreventive effect of memantine in 4T1 tumor-bearing mice.
METHODS
To determine the potential chemopreventive effect of the compound, mice weights, tumor volumes, spleen IL-6, and tumor DNA methylation levels were investigated. A total of 26 Balb/c female mice were allocated into three groups. G1 (n = 6): tumor control group, G2 (n = 10): low dose (5mg/kg) memantine group, G3: high dose (10 mg/kg) memantine group (n = 10). G1 was inoculated with 4T1 cells without any memantine treatment. G2 and G3 were pretreated with 5 and 10 mg/kg memantine daily intraperitoneal (ip) injection (weekend off) for 10 days, respectively. Both G2 and G3 were subdivided into two groups as G2a (n = 4) and G3a (n = 4): tumor free groups and G2b (n = 6) and G3b (n = 6) tumor bearing groups.
RESULTS
Our results revealed that G3: high dose (10 mg/kg) memantine group, significantly (p = 0.0248) reduced the tumor volumes. We found that spleen IL-6 levels were significantly higher in memantine pretreated tumor free group p = 0.0204 ) We also found that high dose memantine treated tumor free group (G3a) has significantly lower genome-wide DNA methylation levels when compared to tumor control group (G1) p = 0.0012.
DISCUSSION
To the best of our knowledge, it is the first study that highlights a potential chemopreventive effect of memantine in vivo in the mouse 4T1 breast tumor model. But further investigations should be carried out to explore the chemopreventive mechanism of action for memantine in cancer.
Topics: Animals; Female; Mice; Memantine; Interleukin-6; Mice, Inbred BALB C; Disease Models, Animal; Injections, Intraperitoneal
PubMed: 36326318
DOI: 10.55730/1300-0144.5381 -
Clinical Interventions in Aging 2009Memantine is an uncompetitive N-methyl-D-aspartate receptor antagonist with moderate affinity. Its mechanism of action is neuroprotective and potentially therapeutic in... (Review)
Review
Memantine is an uncompetitive N-methyl-D-aspartate receptor antagonist with moderate affinity. Its mechanism of action is neuroprotective and potentially therapeutic in several neuropsychiatric diseases. It has been approved by the FDA for the treatment of moderate to severe Alzheimer's disease (AD) either as a monotherapy or in combination with cholinesterase inhibitors. This review covers key studies of memantine's safety and efficacy in treating moderate to severe AD. It also covers current research into other dementias including but not exclusively mild AD and vascular dementia. Other studies on the efficacy of memantine for other neuropsychiatric diseases are discussed. Memantine is a safe and effective drug that merits further research on several topics. Clinicians should be aware of new studies and potential uses of memantine because of its safety and efficacy.
Topics: Alzheimer Disease; Dementia; Dopamine Agents; Humans; Memantine; Severity of Illness Index; Treatment Outcome
PubMed: 19851512
DOI: 10.2147/cia.s6666 -
Expert Opinion on Pharmacotherapy Apr 2011As the world's population ages, the incidence of Alzheimer's disease (AD) is projected to double every 20 years. Understanding the pathogenesis of AD and developing... (Review)
Review
INTRODUCTION
As the world's population ages, the incidence of Alzheimer's disease (AD) is projected to double every 20 years. Understanding the pathogenesis of AD and developing effective treatments is a public health imperative. Memantine is a low- to moderate-affinity, non-competitive NMDA receptor antagonist that is currently approved for the treatment of moderate to severe AD.
AREAS COVERED
We discuss the current evidence, emphasizing more recent studies examining the effects of memantine in AD. We also look at the gaps in the current knowledge; the studies that will be required to fill these gaps are also discussed. The present paper reviews: the pharmacology of memantine; evidence for its use in moderate to severe AD, as well as in mild to moderate AD; adverse events related to memantine use; its effects specifically on behaviours including aggression and agitation; the pharmacoeconomics of memantine; and the use of memantine in other dementias. Memantine has shown modest benefits in cognition, function, global and behavioural measures, and has shown little potential for drug-drug interactions.
EXPERT OPINION
For the treatment of moderate to severe AD, memantine should be offered as a therapeutic option, either on its own, or in combination with a cholinesterase inhibitor.
Topics: Alzheimer Disease; Economics, Pharmaceutical; Excitatory Amino Acid Antagonists; Humans; Memantine; Meta-Analysis as Topic; Neuropsychological Tests
PubMed: 21385152
DOI: 10.1517/14656566.2011.558006 -
International Journal of Clinical... Oct 2020Memantine is currently the only drug that acts on the glutamate energy system to treat Alzheimer's disease. A generic memantine tablet was developed to offer an... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Memantine is currently the only drug that acts on the glutamate energy system to treat Alzheimer's disease. A generic memantine tablet was developed to offer an alternative to the marketed tablet formulation. The purpose of this study was to assess the bioequivalence of two different memantine formulations among healthy male Chinese subjects under fasting and fed conditions.
MATERIALS AND METHODS
We carried out single-center, randomized, single-dose, open-label, two-period, cross-over studies which including 20 healthy male Chinese subjects under fasting and fed conditions, respectively. Plasma samples were collected prior to and up to 240 hours after dosing. Key pharmacokinetic parameters including area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC), area from time zero to infinite (AUC), and C were used for bioequivalence assessment.
RESULTS
Under fasting condition, the 90% CIs of the geometric mean ratios of the test/reference drug for memantine were 106.5 - 114.0% for C, 99.4 - 107.9% for AUC, and 100.0 - 109.6% for AUC. Under fed condition, the 90% CIs of the geometric mean ratios of the test/reference drug for memantine were 94.8 - 104.3% for C, 98.2 - 110.5% for AUC, and 99.2 - 113.0% for AUC.
CONCLUSION
The observed pharmacokinetic parameters of memantine of the test drug were similar to those of the reference formulation both in the fasting and fed state. That is to say, the test formulation of memantine 10-mg tablet is bioequivalent to the reference formulation (Ebixa 10-mg tablet).
Topics: Area Under Curve; Cross-Over Studies; Fasting; Humans; Male; Memantine; Tablets; Therapeutic Equivalency
PubMed: 32729819
DOI: 10.5414/CP203683 -
Fundamental & Clinical Pharmacology Feb 2015Memantine (1-amino-3,5-dimethyladamantane) is a moderate-affinity uncompetitive antagonist of N-methyl-d-aspartate (NMDA) receptors. In this study, we have explored the...
Memantine (1-amino-3,5-dimethyladamantane) is a moderate-affinity uncompetitive antagonist of N-methyl-d-aspartate (NMDA) receptors. In this study, we have explored the effect of memantine against N-methyl-d-aspartate (NMDA)-induced seizures in neonatal rats. Here, we evaluated various behavioral seizure abnormalities in neonatal rats (Sprague-Dawley; postnatal day 9) after an intraperitoneal administration of NMDA. Further, we explored whether an acute administration of memantine could protect these neonates against different phases of convulsions induced by NMDA. In a separate study, we have compared the effect of levetiracetam in the same animal model. Exogenous administration of NMDA (30 mg/kg., i.p.) in neonatal rats resulted in arrest of activity, emprosthotonos curvature (trunk is bent forward by the entire muscles), myoclonic jerks, and forelimb/hindlimb clonus. The clonus phase in neonates was followed by loss of righting reflex and continuous seizures (for more than 5 min) suggesting status epilepticus, tonic extension, and death. Pretreatment of memantine hydrochloride (10-30 mg/kg., i.p.) dose-dependently delayed the onset of different phases of convulsions induced by NMDA. Memantine at the highest dose was found to be ataxic in rat neonates, while lower doses were free of any observed behavioral signs of toxicity. Levetiracetam (25 mg/kg., i.p.) when administered 30 min before the NMDA challenge blocked only the jerk phase and did not affect other phases of NMDA-induced convulsions. These data indicated that memantine and other safer uncompetitive NMDA receptor antagonists may be protective in the management of neonatal seizures.
Topics: Animals; Animals, Newborn; Disease Models, Animal; Female; Male; Memantine; N-Methylaspartate; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Seizures
PubMed: 25196574
DOI: 10.1111/fcp.12090 -
Biochemical and Biophysical Research... Nov 2017Memantine, an uncompetitive glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist, is widely used as a medication for the treatment of Alzheimer's disease (AD)....
Memantine, an uncompetitive glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist, is widely used as a medication for the treatment of Alzheimer's disease (AD). We previously reported that chronic treatment of AD with memantine reduces the amount of insoluble β-amyloid (Aβ) and soluble Aβ oligomers in animal models of AD. The mechanisms by which memantine reduces Aβ levels in the brain were evaluated by determining the effect of memantine on Aβ aggregation using thioflavin T and transmission electron microscopy. Memantine inhibited the formation of Aβ(1-42) aggregates in a concentration-dependent manner, whereas amantadine, a structurally similar compound, did not affect Aβ aggregation at the same concentrations. Furthermore, memantine inhibited the formation of different types of Aβ aggregates, including Aβs carrying familial AD mutations, and disaggregated preformed Aβ(1-42) fibrils. These results suggest that the inhibition of Aβ aggregation and induction of Aβ disaggregation may be involved in the mechanisms by which memantine reduces Aβ deposition in the brain.
Topics: Amyloid beta-Peptides; Dimerization; Memantine; Peptide Fragments; Protein Binding
PubMed: 28917837
DOI: 10.1016/j.bbrc.2017.09.058 -
European Journal of Pharmacology Oct 2019Neurobehavioral bases of tobacco addiction and nicotine reinforcement are complex, involving more than only nicotinic cholinergic or dopaminergic systems. Memantine is...
Neurobehavioral bases of tobacco addiction and nicotine reinforcement are complex, involving more than only nicotinic cholinergic or dopaminergic systems. Memantine is an NMDA glutamate antagonist used to improve cognitive function in people with Alzheimer's disease. Glutamate may be an important component of the reinforcing effects of nicotine, so memantine was evaluated as a potential smoking cessation aid. Two studies were conducted with adult female rats, one testing acute effects of memantine over a range of doses for changing nicotine self-administration and the other testing the chronic effects of memantine to reduce nicotine self-administration. Acute memantine injections slightly, but significantly, increased nicotine self-administration in a dose-related manner. In contrast, chronic memantine treatment significantly reduced nicotine self-administration. During the first day of memantine administration in the chronic study, nicotine self-administration was significantly elevated replicating the acute study. Starting in the second week of treatment there was a significant reduction of nicotine self-administration relative to controls. This was seen because memantine treatment prevented the increase in nicotine self-administration shown by controls. There even continued to be a memantine-induced lowered nicotine self-administration during the week after the cessation of memantine treatment. Memantine or other drugs affecting NMDA glutamate receptors may be useful aids to smoking cessation. Full efficacy for reducing nicotine self-administration was seen as the NMDA drug treatment is given chronically. Importantly, the effect persisted even after treatment is ended, indicating the high potential for NMDA glutamate receptors to impact nicotine addiction.
Topics: Animals; Dose-Response Relationship, Drug; Female; Memantine; Nicotine; Rats; Rats, Sprague-Dawley; Self Administration; Time Factors; Tobacco Use Disorder
PubMed: 31421087
DOI: 10.1016/j.ejphar.2019.172592 -
Molecular Neurobiology Jul 2022Propolis is a complex resinous substance that is relevant as a therapeutic target for Alzheimer's disease (AD) and other neurodegenerative diseases. In this study, we...
Propolis is a complex resinous substance that is relevant as a therapeutic target for Alzheimer's disease (AD) and other neurodegenerative diseases. In this study, we confirmed that propolis (Brazilian green propolis) further enhances the rescue of cognitive deficits by the novel AD drug memantine in APP-KI mice. In memory-related behavior tasks, administration of a single dose of propolis at 1-100 mg/kg p.o. significantly enhanced the rescue of cognitive deficits by memantine at 1 mg/kg p.o. in APP-KI mice. In in vitro studies, propolis significantly increased intracellular Ca concentration and calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation in Kir6.2-overexpressed N2A cells treated with memantine. Propolis also significantly increased adenosine 5'-triphosphate (ATP) contents and CaMKII autophosphorylation, which was impaired in Aβ-treated Kir6.2-overexpressed N2A cells. Similarly, repeated administration of propolis at 100 mg/kg p.o. for 8 weeks further enhanced the rescue of cognitive deficits by memantine in APP-KI mice. Consistent with the rescued cognitive deficits in APP-KI mice, repeated administration of propolis markedly ameliorated memantine-dependent rescue of injured long-term potentiation (LTP) in APP-KI mice, concomitant with increased CaMKII autophosphorylation and calcium/calmodulin-dependent protein kinase IV (CaMKIV) phosphorylation in the hippocampal CA1 region. Furthermore, repeated administration of both memantine and propolis significantly restored the decreased ATP contents in the CA1 region of APP-KI mice. Finally, we confirmed that repeated administration of memantine at 1 mg/kg p.o. and propolis at 100 mg/kg p.o. for 8 weeks failed to restore the cognitive deficits in Kir6.2-/- mice. Our study demonstrates that propolis increases ATP contents and promotes the amelioration of cognitive deficits rescued by memantine via Kir6.2 channel inhibition in the CA1 region.
Topics: Adenosine Triphosphate; Alzheimer Disease; Animals; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cognition; Disease Models, Animal; Memantine; Mice; Mice, Transgenic; Propolis
PubMed: 35587310
DOI: 10.1007/s12035-022-02876-6