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https://www.readbyqxmd.com/read/27920795/donepezil-enhances-frontal-functional-connectivity-in-alzheimer-s-disease-a-pilot-study
#1
Ludovica Griffanti, Gordon K Wilcock, Natalie Voets, Guendalina Bonifacio, Clare E Mackay, Mark Jenkinson, Giovanna Zamboni
BACKGROUND: We have previously shown that increased resting-state functional magnetic resonance imaging (fMRI)-based functional connectivity (FC) within the frontal resting-state networks in Alzheimer's disease (AD) patients reflects residual, possibly compensatory, function. This suggests that symptomatic treatments should aim to enhance FC specifically in these networks. METHODS: 18 patients with probable AD underwent brain MRI and neuropsychological assessment at baseline and after 12 weeks of treatment with donepezil...
September 2016: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/27914299/the-effects-of-fluorine-substitution-on-the-chemical-properties-and-inhibitory-capacity-of-donepezil-anti-alzheimer-drug-density-functional-theory-and-molecular-docking-calculations
#2
Azita Khosravan, Safora Marani, Mohammad Sadegh Sadeghi Googheri
Drug fluorination has the potential to reproduce useful drugs with decreasing the side effect of them. Identifying the effect of this improvement on the chemical properties and biological interactions of drug symbolizes a meaningful progress in drug design. Here the fluorination of Donepezil as an anti-Alzheimer drug, including 7 fluorinated derivatives of it, was investigated computationally. In the first part of our calculations, the most important chemical properties of drug that affects the drug efficiency were investigated by applying the M06/6-31g (d, p) and M062X/6-31g (d, p) levels of theories...
November 25, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/27913166/dose-dependent-effect-of-donepezil-administration-on-long-term-enhancement-of-visually-evoked-potentials-and-cholinergic-receptor-overexpression-in-rat-visual-cortex
#3
Mira Chamoun, Marianne Groleau, Menakshi Bhat, Elvire Vaucher
Stimulation of the cholinergic system tightly coupled with periods of visual stimulation boosts the processing of specific visual stimuli via muscarinic and nicotinic receptors in terms of intensity, priority and long-term effect. However, it is not known whether more diffuse pharmacological stimulation with donepezil, a cholinesterase inhibitor, is an efficient tool for enhancing visual processing and perception. The goal of the present study was to potentiate cholinergic transmission with donepezil treatment (0...
November 29, 2016: Journal of Physiology, Paris
https://www.readbyqxmd.com/read/27911294/deleterious-effect-of-butyrylcholinesterase-k-variant-in-donepezil-treatment-of-mild-cognitive-impairment
#4
Sophie Sokolow, Xiaohui Li, Lucia Chen, Kent D Taylor, Jerome I Rotter, Robert A Rissman, Paul S Aisen, Liana G Apostolova
BACKGROUND: Donepezil is an acetylcholinesterase inhibitor frequently prescribed for the treatment of mild cognitive impairment (MCI) though not approved by the Food and Drug Administration for this indication. In Alzheimer's disease, butyrylcholinesterase (BChE) activity increases with disease progression and may replace acetylcholinesterase function. The most frequent polymorphism of BChE is the K-variant, which is associated with lower acetylcholine-hydrolyzing activity. BChE-K polymorphism has been studied in Alzheimer's disease progression and donepezil therapy, and has led to contradictory results...
November 29, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27901381/effects-of-fisetin-on-hyperhomocysteinemia-induced-experimental-endothelial-dysfunction-and-vascular-dementia
#5
Boyina Hemanth Kumar, Ravula Arun Reddy, Jerald Mahesh Kumar, B Dinesh Kumar, Prakash V Diwan
This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues...
August 11, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27899389/high-dose-rivastigmine-in-the-symptom-management-of-lewy-body-dementia
#6
Joseph Marwan Nour, Leonidas Chouliaras, Lilian Hickey
A man presented in late 2004 at the age of 65 with a decline in memory. He was diagnosed with Lewy body dementia and started on 3 mg rivastigmine a day, which made a marked clinical improvement. He lived with the illness for 10 years, over which time the dose of acetylcholinesterase inhibitors (ChEI) he took rose to two 9.5 mg rivastigmine patches and 7.5 mg donepezil, significantly above British National Formulary (BNF) limits. He demonstrated clear clinical response to ChEI and showed improvements in alertness and functioning...
November 29, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27896785/prescription-patterns-of-medications-for-alzheimer-s-disease-in-japan-from-2010-to-2015-a-descriptive-pharmacy-claims-database-study
#7
Kimiko Kadohara, Izumi Sato, Yuko Doi, Masaru Arai, Yosuke Fujii, Toshiyuki Matsunaga, Koji Kawakami
INTRODUCTION: Although four kinds of Alzheimer's disease (AD) drugs are available at present there was only one drug until 2011 in Japan. This study aimed to elucidate prescription trends of these medications for AD in Japanese outpatients before and after the new drug releases in 2011. METHODS: This descriptive study of pharmacy claims databases analyzed outpatient prescription data from community pharmacies across Japan. The study patients were 20 years or older and first administered medications for AD (donepezil, memantine, rivastigmine, or galantamine) between January 2010 and September 2014...
November 28, 2016: Neurology and Therapy
https://www.readbyqxmd.com/read/27885411/scopolamine-disrupts-place-navigation-in-rats-and-humans-a-translational-validation-of-the-hidden-goal-task-in-the-morris-water-maze-and-a-real-maze-for-humans
#8
Jan Laczó, Hana Markova, Veronika Lobellova, Ivana Gazova, Martina Parizkova, Jiri Cerman, Tereza Nekovarova, Karel Vales, Sylva Klovrzova, John Harrison, Manfred Windisch, Kamil Vlcek, Jan Svoboda, Jakub Hort, Ales Stuchlik
RATIONALE: Development of new drugs for treatment of Alzheimer's disease (AD) requires valid paradigms for testing their efficacy and sensitive tests validated in translational research. OBJECTIVES: We present validation of a place-navigation task, a Hidden Goal Task (HGT) based on the Morris water maze (MWM), in comparable animal and human protocols. METHODS: We used scopolamine to model cognitive dysfunction similar to that seen in AD and donepezil, a symptomatic medication for AD, to assess its potential reversible effect on this scopolamine-induced cognitive dysfunction...
November 24, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27876467/a-review-on-tacrine-based-scaffolds-as-multi-target-drugs-mtdls-for-alzheimer-s-disease
#9
REVIEW
Bilqees Sameem, Mina Saeedi, Mohammad Mahdavi, Abbas Shafiee
Alzheimer's disease (AD) is a multifactorial neurological disorder among elderly people and combinatorial factors such as genetic, lifestyle, and environmental are involved in onset and disease progression. It has been demonstrated that loss of cholinergic transmission is one of the most significant causes of AD. One strategy currently being investigated for the development of new therapeutics relates to the enhancement of cholinergic system through several ways. At this juncture, anticholinesterase inhibitors have absorbed lots of attention and different marketed drugs such as donepezil, rivastigmine, tacrine, and galantamine have been developed...
October 28, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27871793/combining-in-silico-and-in-vitro-approaches-to-evaluate-the-acetylcholinesterase-inhibitory-profile-of-some-commercially-available-flavonoids-in-the-management-of-alzheimer-s-disease
#10
Asokkumar Kuppusamy, Madeswaran Arumugam, Sonia George
The current objective of the study is to identify inhibitory affinity potential of the certain commercially available flavonoids, against crystal structure of acetylcholinesterase (AChE) enzyme using in silico and in vitro studies. The inhibitory profiles of the compounds have been compared with standard AChE inhibitor donepezil. In the docking studies, conformational site analysis and docking parameters like binding energy, inhibition constant and intermolecular energy were determined using AutoDock 4.2. Docking studies conducted with diosmin, silibinin, scopoletin, taxifolin and tricetin exhibited tight binding forces prevailing with the enzyme than between donepezil...
November 18, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27865771/cholinergic-activation-affects-the-acute-and-chronic-antinociceptive-effects-of-morphine
#11
Kinga Gawel, Ewa Gibula-Bruzda, Marcin Dziedzic, Malgorzata Jenda-Wojtanowska, Marta Marszalek-Grabska, Jerzy Silberring, Jolanta H Kotlinska
Current studies indicate that the cholinergic and opioid systems interact to modulate pain. In the present work, we investigated the influence of the cholinesterase inhibitors, donepezil (0.5; 1 or 3mg/kg, i.p.) and rivastigmine (0.03; 0.5 or 1mg/kg, i.p.), on the acute antinociceptive effects of morphine (5mg/kg, i.p.) in the hot plate test in mice. Herein, both inhibitors were found to enhance and prolong the analgesic effects of morphine without affecting latencies themselves. In an extension of this work, we determined which cholinergic receptors subtype mediates the enhancement of analgesic effects of morphine, following inhibition of cholinesterases...
November 16, 2016: Physiology & Behavior
https://www.readbyqxmd.com/read/27858713/protein-expression-of-bace1-is-downregulated-by-donepezil-in-alzheimer-s-disease-platelets
#12
Tamires Alves Sarno, Leda Leme Talib, Helena Passarelli Giroud Joaquim, Jessyka Maria de França Bram, Wagner Farid Gattaz, Orestes Vicente Forlenza
BACKGROUND: Abnormal amyloid-β protein precursor (AβPP) metabolism is a key feature of Alzheimer's disease (AD). Platelets contain most of the enzymatic machinery required for AβPP processing, and correlates of intracerebral abnormalities have been demonstrated in platelets of patients with AD. Thus, AβPP-related molecules in platelets may be regarded as peripheral markers of AD. OBJECTIVE: We sought to determine the protein expression of the AβPP secretases (ADAM10, BACE1, and PSEN1) and AβPP ratio in platelets of patients with mild or moderate AD compared to healthy controls...
November 14, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27855959/assessment-of-the-blood-brain-barrier-permeability-of-potential-neuroprotective-aurones-in-parallel-artificial-membrane-permeability-assay-and-porcine-brain-endothelial-cell-models
#13
Kok-Fui Liew, Nur Aziah Hanapi, Kit-Lam Chan, Siti R Yusof, Chong-Yew Lee
Previously, several aurone derivatives were identified with promising neuroprotective activities. In developing these compounds to target the central nervous system (CNS), an assessment of their blood-brain barrier (BBB) permeability was performed using in vitro BBB models: parallel artificial membrane permeability assay-BBB which measures passive permeability and primary porcine brain endothelial cell model which enables determination of the involvement of active transport mechanism. Parallel artificial membrane permeability assay-BBB identified most compounds with high passive permeability, with 3 aurones having exceptional Pe values highlighting the importance of basic amine moieties and optimal lipophilicity for good passive permeability...
November 14, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27823887/targeting-alzheimer-s-disease-by-investigating-previously-unexplored-chemical-space-surrounding-the-cholinesterase-inhibitor-donepezil
#14
Divan G van Greunen, Werner Cordier, Margo Nell, Chris van der Westhuyzen, Vanessa Steenkamp, Jenny-Lee Panayides, Darren L Riley
A series of twenty seven acetylcholinesterase inhibitors, as potential agents for the treatment of Alzheimer's disease, were designed and synthesised based upon previously unexplored chemical space surrounding the molecular skeleton of the drug donepezil, which is currently used for the management of mild to severe Alzheimer's disease. Two series of analogues were prepared, the first looking at the replacement of the piperidine ring in donepezil with different sized saturated N-containing ring systems and the second looking at the introduction of different linkers between the indanone and piperidine rings in donepezil...
October 20, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27823628/leonurine-ameliorates-cognitive-dysfunction-via-antagonizing-excitotoxic-glutamate-insults-and-inhibiting-autophagy
#15
Chunhua Liu, Hongqiang Yin, Jing Gao, Xiaxia Xu, Tao Zhang, Zhuo Yang
BACKGROUND: Chronic cerebral hypoperfusion is related with cognitive deficits in different types of dementia. PURPOSE: In this study, we aimed to investigate the effect and potential mechanisms of leonurine on chronic cerebral hypoperfusion both in vitro and in vivo. STUDY DESIGN: Chronic cerebral hypoperfusion was duplicated by oxygen-glucose deprivation (OGD) in vitro and by ligation of bilateral common carotid arteries (2-VO) in vivo. METHODS: In in vitro study, there were control group, OGD group, OGD+ 100µM leonurin group, and OGD+ 10µM donepezil group...
December 1, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27822591/-memantine-as-add-on-medication-to-acetylcholinesterase-inhibitor-therapy-for-alzheimer-dementia
#16
R Haussmann, M Donix
Currently available data indicate superior therapeutic effects of combination treatment for Alzheimer dementia with memantine and acetylcholine esterase inhibitors in certain clinical contexts. Out of five randomized, placebo-controlled, double-blind trials two showed superior therapeutic effects in comparison to monotherapy with acetylcholinesterase inhibitors regarding various domains. Recently published meta-analyses and cost-benefit analyses also showed positive results. Recently published German guidelines for dementia treatment also take these new data into account and recommend combination treatment in patients with severe dementia on stable donepezil medication...
November 7, 2016: Der Nervenarzt
https://www.readbyqxmd.com/read/27796293/rapid-and-sustained-cognitive-recovery-in-app-ps1-transgenic-mice-by-co-administration-of-epps-and-donepezil
#17
Hye Yun Kim, Hyunjin Vincent Kim, Dongkeun K Lee, Seung-Hoon Yang, YoungSoo Kim
Alzheimer's disease (AD) is a neurodegenerative disease characterized by sequential progression of pathological events, such as aggregation of amyloid-β proteins, followed by outward symptoms of cognitive impairments. Given that a combination of different therapeutic strategies often provides more rapid and effective outcomes in diverse areas of clinical treatment, we hypothesized that administration of anti-amyloid drugs with cognitive enhancers would result in synergistic effects in AD treatment. Here, we co-administered 4-(2-hydroxyethyl)-1-piperazinepropane-sulphonic acid (EPPS), an amyloid-clearing chemical, and donepezil, an acetylcholinesterase inhibitor, to determine whether they could serve complementary roles for each other in regards to AD treatment...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27790242/the-effects-of-donepezil-on-15-item-geriatric-depression-scale-structure-in-patients-with-alzheimer-disease
#18
Youngsoon Yang, Yong Tae Kwak
BACKGROUND/AIMS: In Alzheimer disease (AD), depression is among the most common accompanying neuropsychiatric symptoms and has different clinical manifestations when compared with early-life depression. In patients with drug-naïve AD, we tried to explore the structure of the 15-item Geriatric Depression Scale (GDS15) and the effect of donepezil on these substructures. METHODS: GDS15, cognitive function, and activities of daily living function tests were administered to 412 patients with probable AD who had not been medicated before visiting the hospital...
September 2016: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/27786552/use-of-antidementia-drugs-and-risk-of-pneumonia-in-older-persons-with-alzheimer-s-disease
#19
Pasi Lampela, Anna-Maija Tolppanen, Antti Tanskanen, Jari Tiihonen, Piia Lavikainen, Sirpa Hartikainen, Heidi Taipale
INTRODUCTION: Persons with Alzheimer's disease are at an increased risk of pneumonia, but the comparative risks during specific antidementia treatments are not known. We compared the risk of pneumonia in use of donepezil, rivastigmine (oral, transdermal), galantamine and memantine. PATIENTS AND METHODS: We used data from a nationwide cohort of community-dwelling individuals diagnosed with Alzheimer's disease during 2005-2011 in Finland, who initiated monotherapy with acetylcholinesterase inhibitor or memantine (n = 65481)...
October 27, 2016: Annals of Medicine
https://www.readbyqxmd.com/read/27785919/pharmacotherapies-for-parkinson-s-disease-symptoms-related-to-cholinergic-degeneration
#20
Santiago Perez-Lloret, María Cecilia Peralta, Francisco J Barrantes
Dopamine depletion is one of the most important features of Parkinson's Disease (PD). However, insufficient response to dopaminergic replacement therapy suggests the involvement of other neurotransmitter systems in the pathophysiology of PD. Cholinergic degeneration contributes to gait impairments, cognitive impairment, psychosis, and REM-sleep disturbances, among other symptoms. Areas covered: In this review, we explore the idea that enhancing cholinergic tone by pharmacological or neurosurgical procedures could be a first-line therapeutic strategy for the treatment of symptoms derived from cholinergic degeneration in PD...
November 7, 2016: Expert Opinion on Pharmacotherapy
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