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Biosensors Aug 2022Fast and reliable determination of enzyme inhibitors are of great importance in environmental monitoring and biomedicine because of the high biological activity and...
Fast and reliable determination of enzyme inhibitors are of great importance in environmental monitoring and biomedicine because of the high biological activity and toxicity of such species and the necessity of their reliable assessment in many media. In this work, a flow-through biosensor has been developed and produced by 3D printing from poly(lactic acid). Acetylcholinesterase from an electric eel was immobilized on the inner walls of the reactor cell. The concentration of thiocholine formed in enzymatic hydrolysis of the substrate was monitored amperometrically with a screen-printed carbon electrode modified with carbon black particles, pillar[5]arene, electropolymerized Methylene blue and thionine. In the presence of thiocholine, the cathodic current at -0.25 V decreased because of an alternative chemical reaction of the macrocycle. The conditions of enzyme immobilization and signal measurements were optimized and the performance of the biosensor was assessed in the determination of reversible (donepezil, berberine) and irreversible (carbofuran) inhibitors. In the optimal conditions, the flow-through biosensor made it possible to determine 1.0 nM-1.0 μM donepezil, 1.0 μM-1.0 mM berberine and 10 nM to 0.1 μM carbofuran. The AChE biosensor was tested on spiked samples of artificial urine for drugs and peanuts for carbofuran. Possible interference of the sample components was eliminated by dilution of the samples with phosphate buffer. Easy mounting, low cost of replaceable parts of the cell and satisfactory analytical and metrological characteristics made the biosensor a promising future application as a point-of-care or point-of-demand device outside of a chemical laboratory.
Topics: Acetylcholinesterase; Berberine; Biosensing Techniques; Carbofuran; Carbon; Donepezil; Electrodes; Enzymes, Immobilized; Methylene Blue; Phosphates; Soot; Thiocholine
PubMed: 36140061
DOI: 10.3390/bios12090676 -
Progress in Neuro-psychopharmacology &... Jul 2024Alzheimer's disease (AD) and depression are inflammatory pathologies, leading to increased inflammatory response and neurotoxicity. Therefore, this study aimed to...
Alzheimer's disease (AD) and depression are inflammatory pathologies, leading to increased inflammatory response and neurotoxicity. Therefore, this study aimed to evaluate the effect of the treatment with fluoxetine and/or galantamine and/or donepezil on the levels of proinflammatory and anti-inflammatory cytokines in a mixed animal model of depression and dementia. Adult male Wistar rats underwent chronic mild stress (CMS) protocol for 40 days and were subjected to stereotaxic surgery for intra-hippocampal administration of amyloid-beta (Aꞵ) peptide or artificial cerebrospinal fluid (ACSF) to mimic the dementia animal model. On the 42nd day, animals were treated with water, galantamine, donepezil, and/or fluoxetine, orally for 17 days. On the 57th and 58th days, the Splash and Y-maze tests for behavior analysis were performed. The frontal cortex and hippocampus were used to analyze the tumor necrosis factor alfa (TNF-α), interleukin 1 beta (IL-1ꞵ), IL-6, and IL-10 levels. The results of this study show that animals subjected to CMS and administration of Aꞵ had anhedonia, cognitive impairment, increased TNF-α and IL-1ꞵ levels in the frontal cortex, and reduced IL-10 levels in the hippocampus. All treatment groups were able to reverse the cognitive impairment. Only donepezil did not decrease the TNF-α levels in the hippocampus. Fluoxetine + galantamine and fluoxetine + donepezil reversed the anhedonia. Fluoxetine reversed the anhedonia and IL-1ꞵ levels in the frontal cortex. In addition, fluoxetine + donepezil reversed the reduction of IL-10 levels in the hippocampus. The results indicate a pathophysiological interaction between AD and depression, and the association of medications in the future may be a possible therapeutic strategy to reduce inflammation, especially the fluoxetine-associated treatments.
Topics: Animals; Male; Rats, Wistar; Disease Models, Animal; Fluoxetine; Donepezil; Rats; Hippocampus; Dementia; Depression; Galantamine; Cytokines; Neuroinflammatory Diseases; Stress, Psychological; Amyloid beta-Peptides; Anhedonia
PubMed: 38552774
DOI: 10.1016/j.pnpbp.2024.110999 -
Recent Patents on Biotechnology 2022Alzheimer's disease (AD) is a kind of neuropsychiatric illness that affects the central nervous system. In this disease, the accumulation of amyloid-beta increases, and... (Review)
Review
Alzheimer's disease (AD) is a kind of neuropsychiatric illness that affects the central nervous system. In this disease, the accumulation of amyloid-beta increases, and phosphorylated tau (P-tau) protein is one of the ways to treat this disease is to reduce the accumulation of amyloid-beta. Various studies have demonstrated that pharmacological approaches have considerable effects in the treatment of AD, despite the side effects and challenges. Cholinesterase inhibitors and the NMDA receptor antagonist memantine are presently authorized therapies for AD. Memantine and Donepezil are the most common drugs for the prevention and therapy of AD with mechanisms such as lessened β-amyloid plaque, affecting N-Methyl-D-aspartate (NMDA) receptors. Diminution glutamate and elevated acetylcholine are some of the influences of medications administrated to treat AD, and drugs can also play a role in slowing the progression of cognitive and memory impairment. A new pharmacological approach and strategy are required to control the future of AD. This review appraises the effects of memantine, donepezil, rivastigmine, and aducanumab in clinical trials, in vitro and animal model studies that have explored how these drugs versus AD development and also discuss possible mechanisms of influence on the brain. Research in clinical trials has substantial findings that support the role of these medications in AD treatment and ameliorate the safety and efficacy of AD therapy, although more clinical trials are required to prove their effectiveness.
Topics: Alzheimer Disease; Animals; Antibodies, Monoclonal, Humanized; Donepezil; Indans; Memantine; Patents as Topic; Piperidines; Rivastigmine
PubMed: 35236274
DOI: 10.2174/1872208316666220302115901 -
Psychosomatics 2018Wernicke's encephalopathy is a condition whose treatment many consultation-liaison psychiatrists know quite well. Less clear, however, is the treatment of its dementia... (Review)
Review
BACKGROUND
Wernicke's encephalopathy is a condition whose treatment many consultation-liaison psychiatrists know quite well. Less clear, however, is the treatment of its dementia disorder descendent, the Korsakoff's syndrome (KS).
OBJECTIVE
This article seeks to review treatment options and provide recommendations for consultation-liaison psychiatrists treating cognitive impairment in KS.
METHODS
In this nonsystematic review, we reviewed PubMed, CINAHL Plus, and Google Scholar for published reports and studies regarding treatment of KS.
RESULTS
The literature revealed case reports and placebo-controlled trials of various medications for treatment of KS, though the samples sizes were small and were mostly case reports. There is more attention devoted toward medications used in other dementia disorders, such as donepezil and memantine. The literature revealed more studies around behavioral interventions recommended for treatment of memory impairment in KS and they focused on cognitive remediation and environmental adaptation, such as the use of PDAs or alarms.
CONCLUSIONS
There is no single, well-studied intervention proven effective as a primary treatment for cognitive impairment in KS. An approach of using environmental modifications in a well-structured living environment, combined with various cognitive interventions, such as pictorial associations, and perhaps a trial of donepezil or memantine, likely represents the best strategy for treating long-term cognitive impairment in KS.
Topics: Cholinesterase Inhibitors; Cognitive Behavioral Therapy; Cognitive Dysfunction; Donepezil; Dopamine Agents; Humans; Korsakoff Syndrome; Memantine; Referral and Consultation; Thiamine; Vitamin B Complex
PubMed: 29751937
DOI: 10.1016/j.psym.2018.03.011 -
Medicine Apr 2024Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial.
OBJECTIVE
The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis.
METHODS
We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results.
RESULTS
All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs.
CONCLUSION
ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated.
Topics: Humans; Alzheimer Disease; Donepezil; Galantamine; Memantine; Molecular Docking Simulation; Cholinesterase Inhibitors; Rivastigmine
PubMed: 38640313
DOI: 10.1097/MD.0000000000037799 -
Die Pharmazie Dec 2020Our aim was to assess the feasibility of transdermal delivery of donepezil and evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of donepezil patch...
Our aim was to assess the feasibility of transdermal delivery of donepezil and evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of donepezil patch and . Donepezil patches were applied to the skin of rabbits and humans for 7 days, then, the PK profiles were observed in a dose-dependent manner. Donepezil was continuously released from the patch for 7 days as compared to oral administration in hairless rats and rabbits. In hairless rats, peak acetylcholinesterase (AChE) inhibition of 34.7±2.0% was observed within 8 h after oral administration of 4 mg/head donepezil, and lasted for less than 24 h, consistent with changes in the plasma donepezil concentration. Peak AChE inhibition by the donepezil patch was equivalent to that in the orally administered group. Donepezil was released continuously from the patch for 7 days with a linear PK in both rats and rabbits. AChE activity inhibition was dependent on donepezil plasma concentration. The data exhibited excellent PK/PD correlation. There was no dermal irritation (erythema/edema) in placebo or donepezil patch group during the study period in minipigs. Thus, Dong-A's donepezil patch appeared to be generally safe and was well tolerated.
Topics: Administration, Cutaneous; Animals; Cholinesterase Inhibitors; Donepezil; Humans; Male; Rabbits; Rats; Skin; Swine; Swine, Miniature; Transdermal Patch
PubMed: 33303060
DOI: 10.1691/ph.2020.0588 -
Clinical Interventions in Aging 2024Genetic variation plays an important role in drug response, there are few relevant studies on patients with Alzheimer's disease continuum (ADC).
BACKGROUND
Genetic variation plays an important role in drug response, there are few relevant studies on patients with Alzheimer's disease continuum (ADC).
OBJECTIVE
This study focused on the associations between two single nucleotide polymorphisms (SNPs) (rs3793790 and rs2177370) located in the CHAT gene and donepezil response in ADC patients, and further evaluated the associations between the two SNPs and ADC.
MATERIAL AND METHODS
According to 2018 National Institute on Aging and Alzheimer's Association (NIA-AA) standard, amyloid β-protein positive (Aβ+) and negative (Aβ-) patients were recruited according to the Aβ-PET/CT standard. rs3793790 and rs2177370 were genotyped in buccal swab samples by using the MassARRAY system. We used the Mini Mental State Examination (MMSE) in Chinese version, caregiver evaluation, and prescribing behavior to assess therapeutic response during the 9-month period. Using logistic regression models, we analyzed the relationship between the two SNPs and donepezil response in 58 Aβ+ patients treated with donepezil alone at the initial diagnosis of ADC. We also explored a probable link between the two SNPs and ADC in 147 Aβ+ and 73 Aβ- patients using a logistic regression analysis.
RESULTS
The chance of donepezil response was higher in patients with the G allele of rs3793790 and/or the A allele of rs2177370 than in those without (odds ratio (OR) 6.83, 95% confidence interval (CI): 1.64-28.49). Additionally, the rs3793790 variant was not associated with ADC, whereas the A allele in rs2177370 increased 1.51-fold the ADC risk (OR 2.51, 95% CI: 1.28-4.95).
CONCLUSION
The genetic variants of rs3793790 and rs2177370 were associated with the donepezil response, and rs2177370 may have a moderate relationship with the risk of ADC.
Topics: Humans; Donepezil; Alzheimer Disease; Polymorphism, Single Nucleotide; Female; Male; Aged; Aged, 80 and over; Genotype; Logistic Models; Cholinesterase Inhibitors; Mental Status and Dementia Tests
PubMed: 38894884
DOI: 10.2147/CIA.S462786 -
British Journal of Pharmacology Dec 2022Donepezil, a piperidine inhibitor of acetylcholinesterase (AChE) prescribed for treatment of Alzheimer's disease, has adverse neuromuscular effects in humans, including...
BACKGROUND AND PURPOSE
Donepezil, a piperidine inhibitor of acetylcholinesterase (AChE) prescribed for treatment of Alzheimer's disease, has adverse neuromuscular effects in humans, including requirement for higher concentrations of non-depolarising neuromuscular blockers during surgery. Here, we examined the effects of donepezil on synaptic transmission at neuromuscular junctions (NMJs) in isolated nerve-muscle preparations from mice.
EXPERIMENTAL APPROACH
We measured effects of therapeutic concentrations of donepezil (10 nM to 1 μM) on AChE enzymic activity, muscle force responses to repetitive stimulation, and spontaneous and evoked endplate potentials (EPPs) recorded intracellularly from flexor digitorum brevis muscles from CD01 or C57BlWld mice.
KEY RESULTS
Donepezil inhibited muscle AChE with an approximate IC of 30 nM. Tetanic stimulation in sub-micromolar concentrations of donepezil prolonged post-tetanic muscle contractions. Preliminary Fluo4-imaging indicated an association of these contractions with an increase and slow decay of intracellular Ca transients at motor endplates. Donepezil prolonged spontaneous miniature EPP (MEPP) decay time constants by about 65% and extended evoked EPP duration almost threefold. The mean frequency of spontaneous MEPPs was unaffected but the incidence of 'giant' MEPPs (gMEPPs), some exceeding 10 mV in amplitude, was increased. Neither mean MEPP amplitude (excluding gMEPPs), mean EPP amplitude, quantal content or synaptic depression during repetitive stimulation were significantly altered by concentrations of donepezil up to 1 μM.
CONCLUSION AND IMPLICATIONS
Adverse neuromuscular signs associated with donepezil therapy, including relative insensitivity to neuromuscular blockers, are probably due to inhibition of AChE at NMJs, prolonging the action of ACh on postsynaptic nicotinic acetylcholine receptors but without substantively impairing evoked ACh release.
Topics: Humans; Mice; Animals; Acetylcholinesterase; Donepezil; Neuromuscular Junction; Synaptic Transmission; Muscle, Skeletal
PubMed: 36028305
DOI: 10.1111/bph.15940 -
Molecular Pharmaceutics Jul 2021Dementia is a significant public health problem in the 21st century. Alzheimer's disease (AD) is an essential factor in dementia. Currently, the drugs used for the... (Review)
Review
Dementia is a significant public health problem in the 21st century. Alzheimer's disease (AD) is an essential factor in dementia. Currently, the drugs used for the treatment of AD are mainly acetylcholine inhibitors (AChEIs). As an AChEI, donepezil (DP) can improve patients' cognitive ability with low side effects and has been accepted by most patients and doctors. For AD patients, the dosage regimen is also crucial due to aging and diseases. Although there are DP oral tablets on the market, there are still many problems to be solved. At present, more and more research is conducted to optimize the route of administration of DP to improve the self-administration of patients. The research fields of DP administration include oral administration, injection administration, intranasal administration, and transdermal administration. This Review is to present the development of different DP administrations and evaluates the advantages and limitations of those works, hoping to optimize the DP dosage regimen for AD patients.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Drug Administration Routes; Drug Delivery Systems; Humans
PubMed: 34100291
DOI: 10.1021/acs.molpharmaceut.1c00290 -
Life Sciences Dec 2020Ischemic stroke remains the leading cause of morbidity and the second most common cause of mortality worldwide. Over the past decade, endovascular thrombectomy (EVT)... (Review)
Review
Ischemic stroke remains the leading cause of morbidity and the second most common cause of mortality worldwide. Over the past decade, endovascular thrombectomy (EVT) drastically changed the care of patients with ischemic stroke due to large vessel occlusion. Nevertheless, despite revascularization, many patients do not achieve a good functional outcome. Moreover, not all patients with ischemic stroke are eligible for EVT. During ischemia, a cascade of ischemic and inflammatory changes lead to permanent damage. As such, adjunct therapies that can protect neurons during acute ischemic phase prior to revascularization have the potential of enhancing functional recovery. Donepezil, an acetylcholinesterase inhibitor, improves cognition and global function in patients with Alzheimer's and Vascular dementia via modulation of acetylcholine receptors and downstream inflammatory response. Preclinical studies demonstrated the potential neuroprotective effects of donepezil in ischemic stroke. However, only a handful of clinical studies investigated this drug's safety and efficacy in stroke patients. In this review, we summarize the current evidence for the utility, or lack thereof, donepezil in treating and rehabilitating patients with ischemic stroke.
Topics: Animals; Cholinesterase Inhibitors; Donepezil; Humans; Ischemic Stroke; Neuroprotective Agents; Recovery of Function
PubMed: 33058916
DOI: 10.1016/j.lfs.2020.118575