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Enrica Cavedo, Bruno Dubois, Olivier Colliot, Simone Lista, Bernard Croisile, Guy Louis Tisserand, Jacques Touchon, Alain Bonafe, Pierre J Ousset, Olivier Rouaud, Fréderic Ricolfi, Alain Vighetto, Florence Pasquier, Samantha Galluzzi, Christine Delmaire, Mathieu Ceccaldi, Nadine Girard, Stéphane Lehericy, Françoise Duveau, Marie Chupin, Marie Sarazin, Didier Dormont, Harald Hampel
OBJECTIVE: Cortical thinning, previously identified during prodromal stages of Alzheimer's disease (AD), is a "candidate" biomarker implemented in AD clinical therapy trials. We investigated the effect of donepezil treatment on cortical thickness in mild cognitively impaired subjects with the amnestic syndrome of the hippocampal type, a prodromal at-risk group for progression to AD dementia. METHODS: Data were from a longitudinal analysis of a community-based multicenter suspected prodromal AD cohort diagnosed by the Free and Cued Selective Reminding Test (81 donepezil vs 92 placebo) enrolled in a double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day)...
October 25, 2016: Journal of Clinical Psychiatry
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
Youngsin Jung, Erik K St Louis
REM sleep behavior disorder (RBD) is a common parasomnia disorder affecting between 1 and 7 % of community-dwelling adults, most frequently older adults. RBD is characterized by nocturnal complex motor behavior and polysomnographic REM sleep without atonia. RBD is strongly associated with synucleinopathy neurodegeneration. The approach to RBD management is currently twofold: symptomatic treatment to prevent injury and prognostic counseling and longitudinal follow-up surveillance for phenoconversion toward overt neurodegenerative disorders...
November 2016: Current Treatment Options in Neurology
Jacques Joubert, Germaine B Foka, Benjamin P Repsold, Douglas W Oliver, Erika Kapp, Sarel F Malan
A series of 7-substituted coumarin derivatives were designed and synthesised to display ChE and MAO-B inhibitory activity. The compounds consisted out of a coumarin structure (MAO-B inhibitor) and benzyl-, piperidine-, N-benzylpiperidine- or p-bromo-N-benzylpiperizine moiety, resembling the N-benzylpiperidine function of donepezil (ChE inhibitor), connected via an alkyl ether linkage at the 7 position. The biological assay results indicated that all the compounds (1-25) displayed selective inhibition to hMAO-B over hMAO-A, with the benzyloxy series (1-8, 10-13) showing nano-molar hMAO-B inhibition (IC50: 0...
September 15, 2016: European Journal of Medicinal Chemistry
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
Sayaka Sasaoka, Toshinobu Matsui, Yuuki Hane, Junko Abe, Natsumi Ueda, Yumi Motooka, Haruna Hatahira, Akiho Fukuda, Misa Naganuma, Shiori Hasegawa, Yasutomi Kinosada, Mitsuhiro Nakamura
Long QT syndrome (LQTS) is a disorder of the heart's electrical activity that infrequently causes severe ventricular arrhythmias such as a type of ventricular tachycardia called torsade de pointes (TdP) and ventricular fibrillation, which can be fatal. There have been no previous reports on the time-to-onset for LQTS based on data from spontaneous reporting systems. The aim of this study was to assess the time-to-onset of LQTS according to drug treatment. We analyzed the association between 113 drugs in 37 therapeutic categories and LQTS including TdP using data obtained from the Japanese Adverse Drug Event Report database...
2016: PloS One
Chandra Bhushan Mishra, Shikha Kumari, Apra Manral, Amresh Prakash, Vikas Saini, Andrew M Lynn, Manisha Tiwari
A novel series of donepezil based multi-functional agents "(E)-5,6-dimethoxy-2-(4-(4-substituted piperazin-1-yl)benzylidene)-2,3-dihydro-1H-inden-1-ones" have been designed and synthesized as potential anti-Alzheimer's agents. In-vitro studies revealed that these compounds demonstrated moderate to good AChE and Aβ aggregation inhibitory activity. These derivatives are also endowed with admirable antioxidant activity. Among the entire series compounds IP-9, IP-13 and IP-15 appeared as most active multi-functional agents and displayed marked AChE inhibitory, Aβ disaggregation and antioxidant activity...
September 19, 2016: European Journal of Medicinal Chemistry
Martin Valis, Jiri Masopust, Oldrich Vysata, Jakub Hort, Rafael Dolezal, Jiri Tomek, Jan Misik, Kamil Kuca, Jana Zdarova Karasova
Although some studies have described the pharmacokinetics and pharmacodynamics of donepezil in the peripheral compartment, studies focused on drug transport across the blood-brain barrier are still very rare. To our knowledge, the fluctuation in the cerebrospinal fluid concentration of donepezil after administration of the drug has not been described in the literature so far. We recruited 16 patients regularly taking a standard therapeutic dose of donepezil (10 mg per day). All patients (Caucasian race) were treated for at least three months with a stable dose of 10 mg per day prior to sample collection...
October 7, 2016: Neurotoxicity Research
Luís F J R Miranda, Karina B Gomes, Pedro A L Tito, Josianne N Silveira, Gerson A Pianetti, Ricardo M D Byrro, Patrícia R H Peles, Fernando H Pereira, Thiago R Santos, Arthur G Assini, Valéria V Ribeiro, Edgar N Moraes, Paulo Caramelli
The clinical response to donepezil in patients with mild and moderate dementia was investigated in relation to the drug plasma concentration and of APOE and CYP2D6 polymorphisms. In a prospective naturalistic observational study, 42 patients with Alzheimer's disease (AD) and AD with cerebrovascular disease who took donepezil (10 mg) for 12 months were evaluated. Their DNA was genotyped, and the donepezil plasma concentrations were measured after 3, 6, and 12 months. Good responders scored ≥-1 on the Mini-Mental State Examination at 12 months in comparison to the baseline score...
October 4, 2016: Journal of Alzheimer's Disease: JAD
Sameer Hassamal, Susan Waller, Kimberly Reese, Claudia Testa
Valproic acid (VPA) is approved by the Food and Drug Administration (FDA) for the treatment of manic or mixed episodes associated with bipolar disorder. VPA is also used off-label to treat other conditions in psychiatry such as impulse control disorders, major depression, and posttraumatic stress disorder (PTSD). Although VPA is mostly well-tolerated, common adverse effects include gastrointestinal symptoms (nausea, vomiting, diarrhea), neurological symptoms (sedation, ataxia, tremor), weight gain, and alopecia...
2016: Türk Psikiyatri Dergisi, Turkish Journal of Psychiatry
Marwan Sabbagh, SeolHeui Han, SangYun Kim, Hae-Ri Na, Jae-Hong Lee, Nagaendran Kandiah, Kammant Phanthumchinda, Chuthamanee Suthisisang, Vorapun Senanarong, Ming-Chyi Pai, Diatri Narilastri, Ajit M Sowani, Encarnita Ampil, Amitabh Dash
BACKGROUND: The 'Asia-Pacific Expert Panel (APEX) for donepezil 23 mg' met in November 2015 to review evidence for the recently approved high dose of donepezil and to provide recommendations to help physicians in Asia make informed clinical decisions about using donepezil 23 mg in patients with moderate-to-severe Alzheimer's disease (AD). SUMMARY: In a global phase III study (study 326) in patients with moderate-to-severe AD, donepezil 23 mg/day demonstrated significantly greater cognitive benefits versus donepezil 10 mg/day, with a between-treatment difference in mean change in the Severe Impairment Battery score of 2...
September 2016: Dementia and Geriatric Cognitive Disorders Extra
B Hemanth Kumar, B Dinesh Kumar, Prakash V Diwan
CONTEXT: Hesperidin (HSP), a flavanoglycone found in citrus fruits, has antioxidant, anti-inflammatory and neuroprotective properties. OBJECTIVE: This study evaluates the protective effect of HSP on l-methionine-induced hyperhomocysteinemia (HHcy) in rats. MATERIALS AND METHODS: Male Wistar rats were randomly divided into seven groups as DMSO, l-methionine, HSP (25, 50 and 100 mg/kg), HSP-per se (100 mg/kg) and donepezil (0.1 mg/kg)...
September 27, 2016: Pharmaceutical Biology
Sean T Stockhausen, Donald Tower
No abstract text is available yet for this article.
September 2016: PM & R: the Journal of Injury, Function, and Rehabilitation
Alfonso Fasano, Silke Appel-Cresswell, Mandar Jog, Mateusz Zurowkski, Sarah Duff-Canning, Melanie Cohn, Marina Picillo, Christopher R Honey, Michel Panisset, Renato Puppi Munhoz
In this review, we have gathered all the available evidence to guide medication management after deep brain stimulation (DBS) in Parkinson's disease (PD). Surprisingly, we found that almost no study addressed drug-based management in the postoperative period. Dopaminergic medications are usually reduced, but whether the levodopa or dopamine agonist is to be reduced is left to the personal preference of the treating physician. We have summarized the pros and cons of both approaches. No study on the management of cognitive problems after DBS has been done, and only a few studies have explored the pharmacological management of such DBS-resistant symptoms as voice (amantadine), balance (donepezil) or gait disorders (amantadine, methylphenidate)...
September 2016: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
Osamu Imamura, Masaaki Arai, Minori Dateki, Kunio Takishima
Oligodendrocytes are the myelin-forming cells of the central nervous system. Oligodendrocyte loss and failure of myelin development result in serious human disorders, including multiple sclerosis. Previously, using oligodendrocyte progenitor cells, we have shown that donepezil, which is an acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease, stimulates myelin gene expression and oligodendrocyte differentiation. Here, we aimed to analyze the effects of donepezil on primary mouse embryonic neural stem cells (NSCs)...
September 24, 2016: Journal of Neurochemistry
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
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
Maria Amat-Foraster, Steven C Leiser, Kjartan F Herrik, Nelly Richard, Claus Agerskov, Christoffer Bundgaard, Jesper F Bastlund, Inge E M de Jong
The 5-HT6 receptor is a promising target for cognitive disorders, in particular for Alzheimer's disease (AD). The high affinity and selective 5-HT6 receptor antagonist idalopirdine (Lu AE58054) is currently in development for mild-moderate AD as adjunct therapy to acetylcholinesterase inhibitors (AChEIs). We studied the effects of idalopirdine alone and in combination with the AChEI donepezil on cortical function using two in vivo electrophysiological methods. Neuronal network oscillations in the frontal cortex were measured during electrical stimulation of the brainstem nucleus pontis oralis (nPO) in the anesthetized rat and by an electroencephalogram (EEG) in the awake, freely moving rat...
September 16, 2016: Neuropharmacology
Mari Paz Serrano, Raquel Herrero-Labrador, Hunter S Futch, Julia Serrano, Alejandro Romero, Ana Patricia Fernandez, Abdelouahid Samadi, Mercedes Unzeta, Jose Marco-Contelles, Ricardo Martínez-Murillo
BACKGROUND: The heterogeneity of Alzheimer disease requires the development of multitarget drugs for treating the symptoms of the disease and its progression. Both cholinergic and monoamine oxidase dysfunctions are involved in the pathological process. Thus, we hypothesized that the development of therapies focused on these targets might be effective. We have developed and assessed a new product, coded ASS234, a multipotent acetyl and butyrylcholinesterase/monoamine oxidase A-B inhibitor with a potent inhibitory effect on amyloid-β aggregation as well as antioxidant and antiapoptotic properties...
September 20, 2016: Journal of Psychiatry & Neuroscience: JPN
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