Memantine for dementia
Memantine has a small beneficial, clinically detectable effect on cognitive function and functional decline measured at 6 months in patients with moderate to severe Alzheimer's Disease (AD). In patients with mild to moderate dementia, the small beneficial effect on cognition was not clinically detectable in those with vascular dementia and barely detectable in those with AD. It is well tolerated. Slightly fewer patients with moderate to severe AD taking memantine develop agitation, but there is no evidence either way about whether it has an effect on agitation which is already present.
Available from: Hamid Charkhkar
- "Memantine has also been reported to be effective in delaying the progress of AD (Gravitz, 2011). An uncompetitive NMDA antagonist, memantine is among the few FDA approved therapeutics for AD (McShane et al., 2006). Although, different hypotheses have been suggested as to how memantine might reduce the detrimental effects of Aβ oligomer, the exact mechanism of action for memantine in relation with AD is still unclear (Danysz and Parsons, 2012; Hu et al., 2007; Song et al., 2008). "
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ABSTRACT: In vitro assays offer a means of screening potential therapeutics and accelerating the drug development process. Here, we utilized neuronal cultures on planar microelectrode arrays (MEA) as a functional assay to assess the neurotoxicity of amyloid-β 1-42 (Aβ42), a biomolecule implicated in the Alzheimer's disease (AD). In this approach, neurons harvested from embryonic mice were seeded on the substrate-integrated microelectrode arrays. The cultured neurons form a spontaneously active network, and the spiking activity as a functional endpoint could be detected via the MEA. Aβ42 oligomer, but not monomer, significantly reduced network spike rate. In addition, we demonstrated that the ionotropic glutamate receptors, NMDA and AMPA/kainate, play a role in the effects of Aβ42 on neuronal activity in vitro. To examine the utility of the MEA-based assay for AD drug discovery, we tested two model therapeutics for AD, methylene blue (MB) and memantine. Our results show an almost full recovery in the activity within 24 hours after administration of Aβ42 in the cultures pre-treated with either MB or memantine. Our findings suggest that cultured neuronal networks may be a useful platform in screening potential therapeutics for Aβ induced changes in neurological function.
Available from: Carlos J Rodriguez-Ortiz
- "In fact, four of the five medications approved by the FDA for prescription to AD patients are aimed to increase extracellular levels of acetylcholine by delaying its degradation (the acetylcholinesterase inhibitors: tacrine, rivastigmine, galantamine and donepezil). The fifth approved drug is memantine, a partial antagonist for the ionotropic glutamate NMDA receptor . Memantine presumably reduces calcium-mediated glutamate excitotoxicity , hence slowing synaptic and neuronal loss characteristically observed in the AD brain . "
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ABSTRACT: Alzheimer's disease (AD) is a leading cause of dementia among elderly. Yet, its etiology remains largely unclear. In this review, we summarize studies that associate systemic infection and neuroinflammation with AD, while highlighting that early-life or life-long exposure to infectious agents predisposes one to develop AD at a later age.
Copyright © 2015. Published by Elsevier Masson SAS.
Available from: Fatemeh Hemmati
- "from excitotoxicity, as a major contributing mechanism to escalating dementia . According to systemic clinical studies on AD patients, Memantine improves cognition  and may reduce behavioral and psychological symptoms of dementia . In spite of the promising results however, Memantine treatment as other currently available ones for AD (Donepezil, Rivastigmine and Galantamine) is symptomatic and does not halt the disease progression , the fact necessitates new drug investigations upon comprehensive knowledge of AD and accompanying dementia. "
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