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William James Deardorff, George T Grossberg
Currently available therapies for the treatment of Alzheimer's disease (AD) consist of cholinesterase inhibitors (ChEIs), such as donepezil, and the N-methyl-D-aspartate receptor antagonist memantine. In December 2014, the US Food and Drug Administration approved Namzaric™, a once-daily, fixed-dose combination (FDC) of memantine extended-release (ER) and donepezil for patients with moderate-to-severe AD. The FDC capsule is bioequivalent to the coadministered individual drugs, and its bioavailability is similar when taken fasting, with food, or sprinkled onto applesauce...
2016: Drug Design, Development and Therapy
Laura M Gault, Robert A Lenz, Craig W Ritchie, Andreas Meier, Ahmed A Othman, Qi Tang, Scott Berry, Yili Pritchett, Weining Z Robieson
BACKGROUND: Results from a phase 2a study indicated that treatment with the novel α7 nicotinic acetylcholine receptor agonist ABT-126 25 mg once daily (QD) was associated with a trend for improvement in cognition in subjects with mild-to-moderate Alzheimer's dementia (AD). A phase 2b program was designed to evaluate a broader dose range of ABT-126 as monotherapy in subjects with mild-to-moderate AD. The program consisted of a double-blind, placebo and active controlled study of ABT-126 (dose range 25-75 mg) and an open-label extension study (75 mg)...
October 18, 2016: Alzheimer's Research & Therapy
Martin Knapp, Derek King, Renée Romeo, Jessica Adams, Ashley Baldwin, Clive Ballard, Sube Banerjee, Robert Barber, Peter Bentham, Richard G Brown, Alistair Burns, Tom Dening, David Findlay, Clive Holmes, Tony Johnson, Robert Jones, Cornelius Katona, James Lindesay, Ajay Macharouthu, Ian McKeith, Rupert McShane, John T O'Brien, Patrick P J Phillips, Bart Sheehan, Robert Howard
OBJECTIVE: Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients. METHODS: Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial...
October 13, 2016: International Journal of Geriatric Psychiatry
Maria Jenelyn M Alviar, Tom Hale, Monalisa Dungca
BACKGROUND: This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable, and disabling. Various medications have been studied in the treatment of phantom pain. There is currently uncertainty in the optimal pharmacologic management of PLP. OBJECTIVES: This review aimed to summarise the evidence of effectiveness of pharmacologic interventions in treating PLP...
October 14, 2016: Cochrane Database of Systematic Reviews
Fleur Harrison, Liesbeth Aerts, Henry Brodaty
Increasing recognition that apathy is one of the most prevalent behavioral and psychological symptoms of dementia and causes substantial caregiver distress has led to trials evaluating psychosocial and pharmacological treatments of apathy in dementia. We evaluated evidence of the efficacy of pharmacotherapies for apathy in dementia from studies since 2013. Previously reported benefits of acetylcholinesterase inhibitors and memantine were not replicated in recent studies. Antidepressants had mixed results with positive effects for apathy shown only for agomelatine, while stimulants, analgesics, and oxytocin study results were inconclusive...
November 2016: Current Psychiatry Reports
Ryan L O'Hare Doig, Carole A Bartlett, Nicole M Smith, Stuart I Hodgetts, Sarah A Dunlop, Livia Hool, Melinda Fitzgerald
Combinations of Ca(2+) channel inhibitors have been proposed as an effective means to prevent excess Ca(2+) flux and death of neurons and glia following neurotrauma in vivo. However, it is not yet known if beneficial outcomes such as improved viability have been due to direct effects on intracellular Ca(2+) concentrations. Here, the effects of combinations of Lomerizine (Lom), YM872, memantine and/or oxATP to block voltage gated Ca(2+) channels, Ca(2+) permeable AMPA receptors, NMDA receptors and purinergic P2X7 receptors (P2X7R) respectively, on Ca(2+) concentration and viability of primary mixed cortical cultures exposed to hydrogen peroxide (H2O2) insult, were assessed...
October 7, 2016: Neuroscience
S I Gavrilova
Alzheimer's disease (AD) is a common neurodegenerative disease with progressive course which leads to severe dementia. The author considers the issues of pathogenesis and diagnosis of AD. The efficacy and safety of memantine are analyzed in depth. Recommendations for clinicians on the use of memantine in patients with AD are presented.
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
J Hara, W R Shankle, L W Barrentine, M V Curole
OBJECTIVES: Studies have produced conflicting results assessing hyperhomocysteinemia (HYH) treatment with B vitamins in patients with normal cognition, Alzheimer's disease and related disorders (ADRD). This study examined the effect of HYH management with L-methylfolate (LMF), methylcobalamin (MeCbl; B12), and N-acetyl-cysteine (CFLN: Cerefolin®/Cerefolin-NAC®) on cognitive decline. DESIGN: Prospective, case-control study of subjects followed longitudinally. SETTING: Outpatient clinic for cognitive disorders...
2016: Journal of Nutrition, Health & Aging
Kamalika Roy, Stephen J Warnick, Richard Balon
No abstract text is available yet for this article.
August 3, 2016: Psychosomatics
Richard A Altschuler, Noel Wys, Diane Prieskorn, Cathy Martin, Susan DeRemer, Sanford Bledsoe, Josef M Miller
Noise overstimulation can induce loss of synaptic ribbons associated with loss of Inner Hair Cell - Auditory Nerve synaptic connections. This study examined if systemic administration of Piribedil, a dopamine agonist that reduces the sound evoked auditory nerve compound action potential and/or Memantine, an NMDA receptor open channel blocker, would reduce noise-induced loss of Inner Hair Cell ribbons. Rats received systemic Memantine and/or Piribedil for 3 days before and 3 days after a 3 hour 4 kHz octave band noise at 117 dB (SPL)...
September 30, 2016: Scientific Reports
Rie Ishikawa, Hotaka Fukushima, Paul W Frankland, Satoshi Kida
Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. Here we show that, following prolonged re-exposure to the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote forgetting of remote contextual fear memory. However, these interventions are ineffective following shorter re-exposures...
2016: ELife
Saigeet Eleti
BACKGROUND: Alzheimer's dementia is one of the most significant health burdens of the modern age in both industrialised and non-industrialised nations as it is a major cause of morbidity and functional impairment in the elderly. Currently there are no cures for progressive dementias, including Alzheimer's disease, and no treatments that would modify their progress. Intervention involves pharmacological treatment to temporarily relieve the symptoms, including three cholinesterase inhibitors and a noncompetitive NMDA antagonist, and the efficacy of these is widely debated...
September 2016: Psychiatria Danubina
Rui Wang, P Hemachandra Reddy
Excitatory glutamatergic neurotransmission via N-methyl-d-aspartate receptor (NMDAR) is critical for synaptic plasticity and survival of neurons. However, excessive NMDAR activity causes excitotoxicity and promotes cell death, underlying a potential mechanism of neurodegeneration occurred in Alzheimer's disease (AD). Studies indicate that the distinct outcomes of NMDAR-mediated responses are induced by regionalized receptor activities, followed by different downstream signaling pathways. The activation of synaptic NMDARs initiates plasticity and stimulates cell survival...
September 23, 2016: Journal of Alzheimer's Disease: JAD
Namrata Singh, Jana Hroudová, Zdeněk Fišar
Impairment of mitochondrial metabolism, particularly the electron transport chain (ETC), as well as increased oxidative stress might play a significant role in pathogenesis of Alzheimer's disease (AD). Some effects of drugs used for symptomatic AD treatment may be related to their direct action on mitochondrial function. In vitro effects of pharmacologically different cognitives (galantamine, donepezil, rivastigmine, 7-MEOTA, memantine) and nootropic drugs (latrepirdine, piracetam) were investigated on selected mitochondrial parameters: activities of ETC complexes I, II + III, and IV, citrate synthase, monoamine oxidase (MAO), oxygen consumption rate, and hydrogen peroxide production of pig brain mitochondria...
September 23, 2016: Molecular Neurobiology
Thomas Desmidt, Caroline Hommet, Vincent Camus
Behavioral and psychological symptoms of dementia (BPSD) are frequent in Alzheimer's disease (AD). They are associated with disability and suffering for both the patients and their caregivers. Even if BPSD are now well diagnosed and characterized by standardized tools, their treatment remains often challenging in clinical setting because of the frequent and severe side effects of the psychotropic drugs when used in this indication. Evidence-based data confirm that antipsychotics and antidepressants are efficient for the treatment of BPSD but have a poor tolerance profile and their use is problematic...
September 1, 2016: Gériatrie et Psychologie Neuropsychiatrie du Vieillissement
Caroline Hommet, Jean-Luc Novella, Sophie Auriacombe, Martine Vercelletto, Gilles Berrut, Serge Belliard, Thomas Desmidt, Mathieu Ceccaldi
Cholinesterase inhibitors and memantine are used from 15 years, in Alzheimer's disease. Benefits have been demonstrated according to cognition, activities of daily living, affective symptoms and behavior, and global impression of change. The aims of this paper are: 1) to describe how these treatments are used in France with a sample survey managed by the national federation of the french CMRR; 2) to study data about efficacy, safety, medicoeconomic impacts and how they are used in Europe.
September 1, 2016: Gériatrie et Psychologie Neuropsychiatrie du Vieillissement
Dong Li, Hongjie Yuan, Xilma R Ortiz-Gonzalez, Eric D Marsh, Lifeng Tian, Elizabeth M McCormick, Gabrielle J Kosobucki, Wenjuan Chen, Anthony J Schulien, Rosetta Chiavacci, Anel Tankovic, Claudia Naase, Frieder Brueckner, Celina von Stülpnagel-Steinbeis, Chun Hu, Hirofumi Kusumoto, Ulrike B S Hedrich, Gina Elsen, Konstanze Hörtnagel, Elias Aizenman, Johannes R Lemke, Hakon Hakonarson, Stephen F Traynelis, Marni J Falk
N-methyl-D-aspartate receptors (NMDARs) are ligand-gated cation channels that mediate excitatory synaptic transmission. Genetic mutations in multiple NMDAR subunits cause various childhood epilepsy syndromes. Here, we report a de novo recurrent heterozygous missense mutation-c.1999G>A (p.Val667Ile)-in a NMDAR gene previously unrecognized to harbor disease-causing mutations, GRIN2D, identified by exome and candidate panel sequencing in two unrelated children with epileptic encephalopathy. The resulting GluN2D p...
October 6, 2016: American Journal of Human Genetics
Angelo M Reggiani, Elena Simoni, Roberta Caporaso, Johann Meunier, Emeline Keller, Tangui Maurice, Anna Minarini, Michela Rosini, Andrea Cavalli
Alzheimer's disease (AD) is a chronic pathological condition that leads to neurodegeneration, loss of intellectual abilities, including cognition and memory, and ultimately to death. It is widely recognized that AD is a multifactorial disease, where different pathological cascades (mainly amyloid and tau) contribute to neural death and to the clinical outcome related to the disease. The currently available drugs for AD were developed according to the one-target, one-drug paradigm. In recent times, multi-target strategies have begun to play an increasingly central role in the discovery of more efficacious candidates for complex neurological conditions, including AD...
2016: Scientific Reports
Ke Zhang, Vitor Nagai Yamaki, Zhisheng Wei, Yu Zheng, Xiang Cai
Evidence from preclinical and clinical studies shows that ketamine, a noncompetitive NMDA receptor antagonist, exerts rapid and sustained antidepressant responses. However, ketamine's psychotomimetic side effects and abuse liability limit the clinical use of the compound. Interestingly, memantine, another NMDA receptor channel blocker, processes no defined antidepressant property but is much safer and clinical tolerated. Understanding why ketamine but not memantine exhibits rapid antidepressant responses is important to elucidate the cellular signaling underlying the fast antidepressant actions of ketamine and to design a new safer generation of fast-acting antidepressants...
January 1, 2017: Behavioural Brain Research
Mohammad-Bagher Ghayour, Arash Abdolmaleki, Morteza Behnam-Rassouli
AIM: Following severe peripheral nerve injury (PNI), regeneration is often insufficient and functional recovery is incomplete. In this regard, glutamate NMDA receptor antagonist such as Memantine have been shown to have neuroprotective effects. We evaluated the effects of Memantine against sciatic nerve crush injury in male Wistar Rats. MATERIAL AND METHODS: Memantine or vehicle was given parenteraly to rats for 7 days postoperative. In Memantine treatment groups, a single dose of agent (5 and 10 mg/kg) was administered daily...
February 5, 2016: Turkish Neurosurgery
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