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Memantine for the treatment of dementia: A review on its current and future applications

dc.contributor.authorFolch J.
dc.contributor.authorBusquets O.
dc.contributor.authorEttcheto M.
dc.contributor.authorSánchez-López E.
dc.contributor.authorCastro-Torres R.D.
dc.contributor.authorVerdaguer E.
dc.contributor.authorGarcia M.L.
dc.contributor.authorOlloquequi J.
dc.contributor.authorCasadesús G.
dc.contributor.authorBeas-Zarate C.
dc.contributor.authorPelegri C.
dc.contributor.authorVilaplana J.
dc.contributor.authorAuladell C.
dc.contributor.authorCamins A.
dc.date.accessioned2020-09-02T22:17:53Z
dc.date.available2020-09-02T22:17:53Z
dc.date.issued2018
dc.identifier10.3233/JAD-170672
dc.identifier.citation62, 3, 1223-1240
dc.identifier.issn13872877
dc.identifier.urihttps://hdl.handle.net/20.500.12728/4488
dc.descriptionAlzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence in the brain of extracellular amyloid-βprotein (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. The N-Methyl-D-aspartate receptors (NMDAR), ionotropic glutamate receptor, are essential for processes like learning and memory. An excessive activation of NMDARs has been associated with neuronal loss. The discovery of extrasynaptic NMDARs provided a rational and physiological explanation between physiological and excitotoxic actions of glutamate. Memantine (MEM), an antagonist of extrasynaptic NMDAR, is currently used for the treatment of AD jointly with acetylcholinesterase inhibitors. It has been demonstrated that MEM preferentially prevents the excessive continuous extrasynaptic NMDAR disease activation and therefore prevents neuronal cell death induced by excitotoxicity without disrupting physiological synaptic activity. The problem is that MEM has shownno clear positive effects in clinical applications while, in preclinical stages, had very promising results. The data in preclinical studies suggests that MEM has a positive impact on improving AD brain neuropathology, as well as in preventing Aβ production, aggregation, or downstream neurotoxic consequences, in part through the blockade of extrasynaptic NMDAR. Thus, the focus of this review is primarily to discuss the efficacy of MEM in preclinical models of AD, consider possible combinations of this drug with others, and then evaluate possible reasons for its lack of efficacy in clinical trials. Finally, applications in other pathologies are also considered. © 2018 - IOS Press and the authors. All rights reserved.
dc.language.isoen
dc.publisherIOS Press
dc.subjectAlzheimer's disease
dc.subjectAmyloid-protein
dc.subjectExtrasynaptic N-Methyl-D-aspartate receptor
dc.subjectMemantine
dc.subjectTau protein
dc.subjectamyloid
dc.subjectapoenzyme
dc.subjectbrain derived neurotrophic factor
dc.subjectcyclin dependent kinase 5
dc.subjectmemantine
dc.subjectn methyl dextro aspartic acid receptor
dc.subjectsynapse receptor
dc.subjectmemantine
dc.subjectneuroprotective agent
dc.subjectAlzheimer disease
dc.subjectclinical feature
dc.subjectclinical trial (topic)
dc.subjectdementia
dc.subjectdiabetes mellitus
dc.subjectdrug effect
dc.subjectdrug efficacy
dc.subjectdrug treatment failure
dc.subjecthuman
dc.subjectinflammation
dc.subjectinsulin metabolism
dc.subjectmodulation
dc.subjectmulticenter study (topic)
dc.subjectneurofibrillary tangle
dc.subjectnonhuman
dc.subjectoxidative stress
dc.subjectpathology
dc.subjectpathophysiology
dc.subjectphase 3 clinical trial (topic)
dc.subjectpreclinical study
dc.subjectpriority journal
dc.subjectprotein phosphorylation
dc.subjectrandomized controlled trial (topic)
dc.subjectReview
dc.subjectAlzheimer disease
dc.subjectanimal
dc.subjectmetabolism
dc.subjectAlzheimer Disease
dc.subjectAnimals
dc.subjectHumans
dc.subjectMemantine
dc.subjectNeuroprotective Agents
dc.titleMemantine for the treatment of dementia: A review on its current and future applications
dc.typeReview


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