Результаты поиска

Donepezil treatment does not improve postoperative delirium, medical, or surgical outcomes following lumbar spine surgery: a propensity-matched analysis.

BACKGROUND CONTEXT: Patients with preoperative cognitive impairment, defined as a diagnosis of dementia or mild cognitive impairment (MCI), have been associated with inferior perioperative lumbar spine surgery outcomes when compared to cognitively normal patients. Donepezil is currently used to improve mentation and memory in patients with cognitive impairment (CI), however there is an absence of literature regarding its impact on postoperative complications following spine surgery. PURPOSE: To assess the impact of Donepezil treatment on postoperative delirium, medical complications, and surg…

Subchronic treatment of donepezil rescues impaired social, hyperactive, and stereotypic behavior in valproic acid-induced animal model of autism.

Autism spectrum disorder (ASD) is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model). We found that prenatal exposure of valproic acid (VPA) induced dysregulation of cholinergic neuronal dev…

Vagus nerve stimulation and acetylcholinesterase inhibitor donepezil provide cardioprotection against trastuzumab-induced cardiotoxicity in rats by attenuating mitochondrial dysfunction.

Trastuzumab (Trz) is a targeted anticancer drug for human epidermal growth factor receptor 2 (HER2)-positive tumors, as Trz-induced cardiotoxicity (TIC) is commonly observed in Trz-treated patients. Since cardiac autonomic modulation with electrical vagus nerve stimulation (VNS) and acetylcholinesterase (AChE) inhibitors exerts cardioprotection against various heart diseases, the comparative effects of electrical VNS and an AChE inhibitor (donepezil) on cardiac and mitochondrial functions and programmed cell death pathways in TIC are not known. VNS devices were implanted in thirty-two male Wis…

Adding the acetylcholinesterase inhibitor, donepezil, to losartan treatment markedly improves long-term survival in rats with chronic heart failure.

AIMS: Modulation of vagal tone using electrical vagal nerve stimulation or pharmacological acetylcholinesterase inhibition by donepezil exerts beneficial effects in an animal model of chronic heart failure (CHF). Considering different treatment mechanisms underlying renin-angiotensin system (RAS) suppression and parasympathetic activation, we hypothesized that parasympathetic activation together with RAS inhibition could attenuate CHF progression. To test this hypothesis, we investigated the therapeutic effects of a combination of donepezil and losartan in CHF rats with extensive myocardial in…

Design, synthesis and biological evaluation of donepezil-safinamide hybrids as dual AChE and MAO-B inhibitor for Alzheimer's disease treatment.

Alzheimer's disease (AD) still lacks therapies that definitively halt its progression. Dual AChE/MAO-B inhibitors offer a promising strategy to address both symptoms and pathology. Here, we designed and synthesised a series of donepezil-safinamide hybrids. The optimised compound 28c was identified as a potent inhibitor of AChE (IC50 = 1.70 μM) and MAO-B (IC50 = 0.18 μM). Mechanistic studies indicated that 28c acts as a reversible mixed-type inhibitor of AChE and a competitive reversible inhibitor of MAO-B. Molecular docking and molecular dynamic simulations revealed that 28c could strongly and…

Age-dependent remodeling of the sciatic proteome in 5xFAD mice can be attenuated by exercise or donepezil treatment to maintain neuromuscular function.

UNLABELLED: Background: Alzheimer's disease (AD) progresses along a continuum for years to possibly decades prior to cognitive decline and c … therefore limiting interventional capacity. We hypothesized that either voluntary wheel running or donepezil treatment, begun prior to neuromuscular decline, would delay manifestation of neuromuscular impairment in 5xFAD mice. Methods: Sciatic nerves from 5xFAD and wild-type (WT) mice were analyzed by tandem mass tag (TMT)-labeled proteomics at 3, 4, and 7 …

The impact of CYP2D6 on donepezil concentration and its lack of effect on the treatment response and adverse effect in Korean patients with Alzheimer's disease.

Donepezil, an acetylcholinesterase inhibitor, is widely used for managing the symptoms of Alzheimer's disease (AD), yet its clinical response varies widely among individuals. This study aims to investigate the influence of CYP2D6 genetic variants on donepezil concentration, treatment response, and adverse effects in Korean patients with AD dementia. We conducted a longitudinal study involving 76 patients receiving either 5 mg or 10 mg of donepezil. Genetic testing identified 9 CYP2D6 alleles, categorizing patients by metabolizing abilities. Blood sampling for plasma concentrations of donepezil…

Disease-modifying treatment with I2 imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: a comparative study with donepezil.

BACKGROUND AND PURPOSE: The development of effective therapeutic strategies against Alzheimer's disease (AD) remains a challenge. I2 imidazoline receptor ligands have a neuroprotective role in AD. Moreover, co-treatment of AChE inhibitors with neuroprotective agents have shown better effects on the prevention of dementia. Here, we assessed the potential therapeutic effect of the I2 ligand, donepezil and their combination in 5XFAD mice. EXPERIMENTAL APPROACH: 5XFAD female mice were treated with low doses (1 mg·kg-1 ·day-1 ) of LSL60101, donepezil and donepezil plus LSL60101, during 4 weeks per…

Analysis of electropharmacological and proarrhythmic effects of donepezil using the halothane-anesthetized intact dogs and the conscious chronic atrioventricular block ones.

Donepezil, an inhibitor for acetylcholinesterase used for patients with Alzheimer's disease, has been shown to inhibit IKr, occasionally inducing torsade de pointes. In order to analyze the causal relationship between donepezil treatment and onset of lethal arrhythmias, we initially assessed electropharmacological effects of donepezil hydrochloride of 0.01, 0.1, and 1 mg/kg, i.v. over 10 min using the halothane-anesthetized intact dogs (n = 4), possibly providing subtherapeutic to supratherapeutic plasma concentrations. Although the low or middle dose did not exert any effect, the high dose tr…

Differential blockade by huperzine A and donepezil of sympathetic nicotinic acetylcholine receptor-mediated nitrergic neurogenic dilations in porcine basilar arteries.

Nicotinic acetylcholine receptor activation on the perivascular sympathetic nerves via axo-axonal interaction mechanism causes norepinephrine release, which triggers the neurogenic nitrergic relaxation in basilar arteries to meet the need of a brain. Donepezil and huperzine A, which are the cholinesterase inhibitors used for Alzheimer's disease therapy, exert controversial effects on nicotinic acetylcholine receptors. Therefore, we investigated how donepezil and huperzine A via the axo-axonal interaction regulate the neurogenic vasodilation of isolated porcine basilar arteries and define their…

Hippocampal Proteomic Alteration in Triple Transgenic Mouse Model of Alzheimer's Disease and Implication of PINK 1 Regulation in Donepezil Treatment.

Donepezil is a clinically approved acetylcholinesterase inhibitor (AChEI) for cognitive improvement in Alzheimer's disease (AD). Donepezil has been used as a first-line agent for the symptomatic treatment of AD, but its ability to modify disease pathology and underlying mechanisms is not clear. We investigated the protective effects and underlying mechanisms of donepezil in AD-related triple transgenic (APPSwe/PSEN1M146V/MAPTP301L) mouse model (3×Tg-AD). Mice (8-month old) were treated with donepezil (1.3 mg/kg) for 4 months and evaluated by behavioral tests for assessment of cognitive functio…

Donepezil-Based Central Acetylcholinesterase Inhibitors by Means of a "Bio-Oxidizable" Prodrug Strategy: Design, Synthesis, and in Vitro Biological Evaluation.

With the aim of reducing side effects of acetylcholinesterase inhibitors (AChEIs) during symptomatic treatment of Alzheimer's disease, we report herein a new class of donepezil-based "bio-oxidizable" prodrugs 1 designed to be converted into dual binding site AChEIs 2. While most of indanone-derived N-benzylpyridinium salts 2 revealed to be highly potent dual binding site hAChEIs (IC50 up to 3 nM), outperforming the standard drug donepezil (IC50 = 11 nM), most of the corresponding 1,4-dihydropyridines 1 were found to be inactive. Promisingly, whereas the selected prodrug 1r showed good permeabi…

Synergistic enhancing-memory effect of donepezil and S 47445, an AMPA positive allosteric modulator, in middle-aged and aged mice.

Positive allosteric modulators of AMPA receptors (AMPA-PAMs) are described to facilitate cognitive processes in different memory-based model … 445 also reversed the age-induced deficit at all tested doses (from 0.03 to 0.3 mg/kg, p.o.). Since donepezil, an acetylcholinesterase inhibitor, induces only moderate symptomatic effects on memory in Alzheimer's disease patients, an alternative strategy for treatment of cognitive symptoms could be to act simultaneously on both glutamatergic AMPA receptors …

A randomized, 4-week double-blind placebo control study on the efficacy of donepezil augmentation of lithium for treatment of acute mania.

INTRODUCTION: A significant number of mania patients fail to respond to current pharmacotherapy, thereby there is need for novel augmentation strategies. The results of some early studies showed the effectiveness of cholinomimetics in the treatment of mania. One open case series suggested the efficacy of donepezil in the treatment of bipolar disorder. Our aim was to explore whether an oral cholinesterase inhibitor, donepezil, administered during a 4-week treatment period, would benefit patients with acute mania. METHODS: We conducted a 4-week double-blind, placebo-controlled trial of donepezi…

Variability of AChE, BChE, and ChAT genes in the late-onset form of Alzheimer's disease and relationships with response to treatment with Donepezil and Rivastigmine.

Several factors are believed to give rise to the late onset sporadic form of Alzheimer's disease (LOAD). We have studied the variation at th … nal study concerning the possible role of the genetic composition on the efficacy of treatment with Donepezil and Rivastigmine. We related the SNPs of the above cited genes with cognitive status measured by MMSE. Carrying an allele or a genotype of these SNPs does not seem to play a relevant role in the response to treatment with the two cholinesterase inhi …

Модуляция ацетилхолинового уровня при помощи гидрохлорида dopezil смягчает остроту экспериментального аутоиммунного энцефаломиелита (EAE) — животной модели множественного склероза.

Множественный склероз (MS) — хроническая аутоиммунная болезнь, характеризующаяся нейроинфламмацией и обезвоживанием, без какого-либо лечения. Предыдущие исследования показали, что кротоксин, нейротоксин, полученный из яда гремучих змей, эффективно смягчает гиперальгезию и клинические симптомы экспериментального аутоиммунного энцефаломиелита (EAE), в сочетании с силикой SBA-15 (CTX-SBA-15), инертной наноструктурной частицой. Эта комбинация затормозила развитие болезни и уменьшила нейронную воспаление. Опираясь на эти результаты, мы провели всеобъемлющий анализ выражения генов для выявления дифф

Совпадение в аннотации оригинала
Multiple sclerosis (MS), is a chronic autoimmune disease characterized by neuroinflammation and demyelination, with no known cure. Previous … ation analysis highlighted acetylcholine receptors pathways as significant targets. For validation, donepezil hydrochloride, an acetylcholinesterase inhibitor, was administered (2 mg/kg/day) initiating 12 days after immunization, with body weight monitored every other day. Donepezil improved clinical symptoms, reduced weight loss, decreased cellular infiltr …

Effect of woohwangchungsimwon and donepezil co-treatment on cognitive function and serum metabolic profiles in a scopolamine-induced model of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Woohwangchungsimwon (WCW) is a traditional medicine used in East Asian countries to treat central nervous system disorders. Reported pharmacological properties include antioxidant effects, enhanced learning and memory, and protection against ischemic neuronal cell death, supporting its use in treating neurodegenerative diseases like Alzheimer's disease (AD). AIM OF THE STUDY: The study aims to assess the effects of co-treatment with WCW and donepezil on cognitive functions and serum metabolic profiles in a scopolamine-induced AD model. MATERIALS AND METHODS: C…

Modulation of Brain Activity and Functional Connectivity by Acupuncture Combined With Donepezil on Mild-to-Moderate Alzheimer's Disease: A Neuroimaging Pilot Study.

BACKGROUND: Functional brain imaging changes have been proven as potential pathophysiological targets in early-stage AD. Current longitudina … The forty-four patients with AD received a 12-week intervention of either acupuncture combined with Donepezil (the treatment group) or Donepezil alone (the control group). The two groups received two functional magnetic resonance imaging (fMRI) scans before and after treatment. The healthy subject group underwent no intervention, and only one fMRI scan was …

Donepezil alone and combined with intensive language-action therapy on depression and apathy in chronic post-stroke aphasia: A feasibility study.

This study explored the feasibility and effectiveness of a short-term (10-week) intervention trial using Donepezil administered alone and combined with intensive language action therapy (ILAT) for the treatment of apathy and depression in ten people with chronic post-stroke aphasia. Outcome measures were the Western Aphasia Battery and the Stroke Aphasia Depression Questionnaire-21. Structural magnetic resonance imaging and 18fluorodeoxyglucose positron emission tomography were acquired at baseline and after two endpoints (Donepezil alone and Donepezil-ILAT). The intervention was found to be f…