جستجوی مقالات مرتبط با کلیدواژه « donepezil » در نشریات گروه « پزشکی »

Donepezil [Aricept®] is a centrally acting reversible acetylcholinesterase inhibitor. We are reporting an unusual case of a 49-year-old male patient with a history of gastric bypass surgery who mistakenly ingested 200 mg of donepezil. During the hospital stay, atypical presentations such as tachycardia, disorientation, mydriasis, and ophthalmic myoclonus were diagnosed. He had experienced convulsions several times and developed rhabdomyolysis. The patient gradually improved under supportive management and was discharged from the hospital after seven days. The authors hope that reporting this case will provide both context for clinicians to be aware of its overdose that may be presented by atypical manifestations or side effects, along with the main muscarinic anticholinergic presentations.

The present investigation has been done to study the behavioral effects of donepezil in autistic children, given that not much research has been carried out concerning using this drug for treating autism.

A cross-sectional and analytic-descriptive study was done on twentypatients with autism, aged 4-17, who visited the neurology clinic of Gorgan’s Taleghani Pediatric Hospital and Yasha Pediatric Autism Clinic, Iran from 2019 to 2020. Demographic information, including sex, age, father’s education, mother’s education ,patient’s education, family status, other problems, and ethnicity, were documented using a checklist, having been filled in during interviews with the parents. Before the trial, ABC cognitive and behavioral tests were taken to determine the children’s current status. After the tests, these children received a daily dose of donepezil (10mg) before sleep for three months. At the end of the three months, the cognitive and behavioral tests were taken from the children once again. In order to analyze the effects of different factors on the studied variables, including irritability, lethargy, stereotypic behavior, hyperactivity, and inappropriate speech before and after the administration of donepezil in patients, a generalized linear model and to test the effects of donepezil on the studied variables, paired t-test was used.

In this study, twenty patients were registered for the investigation, 12 (60%) male and eight (40%) female. Age groups 5-6 had the highest frequency, and age group 17 had the lowest. Regardingthe parents’ education, the highest frequency was for bachelor’s degrees, and the lowest was for less-than-high school education and master’s degree. The highest frequency for the patients’ education was kindergarten (60%), and then groups without education (20%) and elementary school-level education (15%). Most of the studied patients (80%) did not have other problems besides autism, and only 20% had other problems besides autism. The family status of 15% of the families was ‘separated,’ and ethnically, most patients (80%) were Fars, while the rest (20%) were Turkmen. None of the analyzed factors (age, sex, father’s education, mother’s education, patient’s education, other problems, family status, and ethnicity) had a significant effect on the studied variables after the administration of donepezil. Among the studied variables prior to the administration of donepezil and among the analyzed factors, the father’s education, the patient’s education, other problems, and family status had only a significant effect on stereotypic behavior. The present research findings of the present research indicated that all the studied variables, including irritability, lethargy, stereotypic behavior, hyperactivity, and inappropriate speech, were significantly decreased toward the desired goal. The decreased amounts in irritability, lethargy, stereotypic behavior, hyperactivity, and inappropriate speech after the administration of donepezil were, respectively, 38%, 44%, 54%, 41%, and 54% and on average, these behaviors were reduced by 46%.

The present investigation has shown that all the studied variables, including irritability, lethargy, stereotypic behavior, hyperactivity, and inappropriate speech, were significantly decreased towards the desired goal by 46%. This significant decrease is indicative of the effectiveness of the treatment of autism patients with donepezil, and therefore, this drug can be placed as a prominent and essential part of the medical therapy of autism.

Donepezil, a noncompetitive acetylcholinesterase inhibitor, is prescribed to treat mild to moderate Alzheimer's disease but it only has moderate performance. Therefore, combination therapies are more effective. There is much evidence suggesting that statins have neuroprotective effects on neurological disorders including Alzheimer's disease. The present study aimed to investigate the combined effects of Donepezil and Lovastatin on the activity of the pyramidal neurons of the CA1 hippocampus. In the present experiment study, adult male rats were divided into 3 groups: Nucleus Basalis Magnocellularis (NBM) lesion (which received electrically- induced lesion (0.5 mA, 3s) in NBM) group, NBM lesion + injection Donepezil 5mg/kg-Lovastatin 10mg/kg, NBM lesion+ injection Donepezil 15mg/kg-Lovastatin 30mg/kg. Spontaneous activity of pyramidal neurons in CA1 region to injection of Donepezil-Lovastatin was investigated in a rat model of Alzheimer's disease. The results of this study showed that electrical lesion of NBM leads to a decrease in the activity frequency of pyramidal neurons in the CA1 region. Administration of Donepezil 5mg/kg-Lovastatin 10mg/kg increased the frequency of pyramidal neurons in rat model of Alzheimer's disease. The results of this study suggest that co-administration of Donepezil-Lovastatin (low doses) increases the activity of the CA1 pyramidal neurons in a rat model of Alzheimer’s disease.

Conventional medicines for Alzheimer’s disease (AD) have little efficacy and are linked to several severe effects, necessitating alternative therapy. The current study investigated the memory-enhancing effects and antioxidant activities of stem bark and leaf MeOH extracts of Prunus africana in scopolamine-induced amnesic mice. Several inclusions build up in brain tissue during AD progression and the brain clears them oxidatively. This makes the antioxidant activity a vital requirement for plant extracts that are used with great success to manage AD.

In this study, for each plant extract, thirty Swiss albino mice were randomly assigned to six groups; extract-treated, reference drug control, normal control, and negative control groups. The mice were then subjected to the Morris water maze task for four consecutive days, euthanized and their whole brains were assessed for antioxidant activities.

The studied extracts significantly (P < 0.01) reduced escape latencies of experimental mice in a dose-related manner, depicting their considerable memory-enhancing effects. The extracts also displayed significant (P < 0.01) enzymatic and non-enzymatic antioxidant activities.

The leaf and stem bark MeOH extracts of P. africana possess phytocompounds with spatial memory-enhancing effects and antioxidant activities.

Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer's disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson's disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer's and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer's diseases, and more comprehensive studies are needed.

Alzheimer disease is a progressive and irreversible disease that finally leads to death. It destroys cognitive skills and memory, and eventually, the patient cannot do the simplest things.

Cholinesterases (ChEs) which has the capability to control cholinergic transmission would result in elevating acetylcholine levels in the brain, by inhibiting CHEs. Coumarins have been shown to exhibit the inhibitory effect of cholinesterase, where the aromatic component results in designing novel candidates that can inhibit Ab accumulation.

The condensation of aryl aldehydes and 4-hydroxycoumarin. Besides, we applied ZnO nanoparticles as an effective heterogeneous catalyst in [bmim]BF4. To determine the inhibitory activity, we used a substrate, i.e., acetylthiocholine iodide, to assay the tested compounds. Moreover, we applied Ellman’s assay.

The present research is an in vitro work. It explores the possible binding mode of these compounds inside the Acetylcholinesterase (AChE) enzyme. Moreover, regarding the synthesized coumarin derivatives, we also performed docking and Molecular Dynamics (MD) simulation studies. The results indicate a satisfactory inhibitory activity for the assayed compounds against AChE with IC50 values from 0.100 to 0.02 µM. In this sense, the stability of protein-ligand complexes and the interaction of the compounds can be understood by performing a molecular docking with molecular dynamics simulation of 5000 ps in the solvent system for AChE. 

Finally, it is worth mentioning that we also tested coumarin derivatives (L14 and L15), leading to potent and effective AChE inhibitors.

This study aimed to evaluate the impact of resistance exercise and donepezil on some neurotrophins gene expression and Trk receptors in the hippocampus of rats with Alzheimer’s disease (AD).

In this study, 32 male adult Wistar rats (mean weight: 230 - 280 g) were assigned into two groups of AD and control. The control and AD groups received normal saline and streptozotocin (STZ) through intraventricular injection, respectively. Then, six subgroups were considered: (1) control rest (Con); (2) control exercise (Con-Exe); (3) Alzheimer’s rest (Alz); (4) Alzheimer’s exercise (Alz-Exe); (5) Alzheimer’s donepezil (Alz-Don); and (6) Alzheimer’s donepezil-exercise (Alz-Don-Exe). Donepezil was fed daily at a dose of 1.5 mg/kg to the treated groups. The three subgroups of exercising rats received exercises for eight weeks (three times a week). Each day, the resting groups were managed to decrease stress impacts. Twenty-four hours after the last session of exercise by the eighth week, deep anesthesia was applied, and the rats' heads were severed.

Considering an error rate below 5% (P < 0.05) and a confidence of more than 95%, a significant difference was observed in BDNF, NT3, NGF, TrkA, and TrkB values between exercising and donepezil-exercise rats compared to AD group. These values were considerably greater for donepezil-exercising Alzheimer’s group. Besides, the donepezil group was not significantly different from the Alzheimer’s group.

Although the use of donepezil alone did not significantly increase the expression of the studied genes, the concomitant use of the drug and resistance training significantly increased the expression levels.

 Electroconvulsive therapy (ECT) is an effective strategy in the treatment of mood disorders; however, it is associated with some cognitive complications.

 This study aimed to evaluate the efficacy of donepezil as an acetylcholinesterase inhibitor in improving cognitive impairment induced by ECT in mood disorder patients.

 Ninety-six mood disorder patients were randomly assigned to the donepezil (5mg/day) or placebo groups. The Persian versions of the Mini-Mental Status examination (MMSE) and Addenbrooke’s Cognitive Examination Revised (ACE-R) were used to evaluate cognitive performance before the first ECT session, after the fourth ECT session, and four weeks after the last ECT session.

 The mean scores of MMSE and ACE-R revealed significant improvement in the donepezil group over time (P < 0.001). All ACE-R subscales increased significantly following the intervention implementation in the donepezil group (P < 0.001). Furthermore, the donepezil group reported no remarkable complications and completed the study.

 Donepezil co-administration with ECT may improve the ECT-induced cognitive disturbances.

Alzheimer disease (AD) is the most common age‑dependent dementia. The complex natural accumulation of amyloid beta (Aβ) precursor protein in hippocampus neurons is regarded as the earliest pathological feature of AD, although there are cholinergic assumptions and effective inflammation in AD. In this animal experimental study, we evaluated the preventive effect of hyoscyamoside (Hyo) and donepezil (Dz) on plaque formation and improvement of neurogenic inflammation in AD rats.

Dz was prepared and Hyo (steroidal saponin) was isolated from Hyoscymus niger. Then, Wistar rats divided into five groups including negative and positive controls, AD, Dz, and Hyo treatment groups based on the drug exposure and their behavioral alternation was examined using Morris water maze (MWM) test. Bielschowsky staining was used to detect the nerve fibers. Serum levels of interleukin (IL)‑4 and IL‑6 were evaluated by ELISA. The RNA expression of cyclin‑dependent kinase CDK11-P58 in peripheral blood lymphocytes was performed using quantitative PCR.

The MWM test showed significant changes in time the models spent to find the hidden platform. The Hyo treatment group showed a notable speed change (P < 0.01). The histopathological analysis of the hippocampal tissue revealed the inhibition of Aβ formation in the treatment groups. The treatment groups had a significant decline in the serum level of IL‑6, and the IL‑4 serum level was increased in the Hyo and Dz treated groups. The expression levels of CDK11-P58 was significantly decreased in the treatment groups.

In sum, the therapeutic effects of Hyo is comparable with that of Dz in AD rats by suppressing neuroinflammation. Thus, these compounds could be considered as a preventive agent in the AD therapy

< p>Computer-aided drug design provides broad structural modifications to evolving bioactive molecules without an immediate requirement to observe synthetic restraints or tedious protocols. Subsequently, the most promising guidelines with regard to synthetic and biological resources may be focused on upcoming steps. Molecular docking is common in-silico drug design techniques since it predicts ligand-receptor interaction modes and associated binding affinities. Current docking simulations suffer serious constraints in estimating accurate ligand-receptor binding affinities despite several advantages and historical results. Response surface method (RSM) is an efficient statistical approach for modeling and optimization of various pharmaceutical systems. With the aim of unveiling the full potential of RSM in optimizing molecular docking simulations, this study particularly focused on binding affinity prediction of citalopram-serotonin transporter (SERT) and donepezil-acetyl cholinesterase (AChE) complexes. For this purpose, Box-Behnken design of experiments (DOE) was used to develop a trial matrix for simultaneous variations of AutoDock4.2 driven binding affinity data with selected factor levels. Responses of all docking trials were considered as estimated protein inhibition constants with regard to validated data for each drug. The output matrix was subjected to statistical analysis and constructing polynomial quadratic models. Numerical optimization steps to attain ideal docking accuracies revealed that more accurate results might be envisaged through the best combination of factor levels and considering factor interactions. Results of the current study indicated that the application of RSM in molecular docking simulations might lead to optimized docking protocols with more stable estimates of ligand-target interactions and hence better correlation of in-silico in-vitro data.

Current palliative pharmacotherapy of Alzheimer’s disease based on the cholinergic hypothesisled to the development of four cholinesterase inhibitors. These compounds can bring prolongationof the symptom-free period in some patients. This is the frst report directly comparing donepeziland rivastigmine plasma and brain levels in in-vivo study. Donepezil and rivastigmine wereapplied i.m. to rats; the dose was calculated from clinical recommendations. The samples wereanalysed on an Agilent 1260 Series LC with UV/VIS detector. An analytical column (WatersSpherisorb S5 W (250 mm × 4.6 i.d.; 5 μm particle size)) with guard column (Waters SpherisorbS5 W (30 mm × 4.6 mm i.d.)) was used. The mobile phase contained acetonitrile and 50 mMsodium dihydrogen phosphate (17:83; v/v); pH 3.1. The LLOQ in rat plasma was 0.5 ng/mL fordonepezil and 0.8 ng/mL for rivastigmine, and the LLOQ in rat brain was 1.0 ng/mL for donepeziland 1.1 ng/mL for rivastigmine. Both compounds showed ability to target the central nervoussystem, with brain concentrations exceeding those in plasma. Maximum brain concentration afteri.m. administration was reached in the 36 (8.34 ± 0.34 ng/mL) and 17 minute (6.18 ± 0.40 ng/mL),respectively for donepezil and rivastigmine. The differences in brain profle can be most easilyexpressed by plasma/brain AUCtotal ratios: donepezil ratio in the brain was nine-times higher thanin plasma and rivastigmine ratio was less than two-times higher than in plasma.

Background:

Cognitive impairment is one of the debilitating consequences of multiple sclerosis (MS) with negative effects on daily life, individual and social activities, quality of life (QOL), and depression. No approved medication is introduced so far for affected individuals. We aimed to evaluatethe efficacy of donepezil on cognitive performance, QOL, and depression in MS.

Methods:

This is a double‑blinded randomized clinical trial conducted on 100 patients with MS during 2018. Patients were assessed prior to intervention abbreviated mental test (AMT), prospective and retrospective mental questionnaire (PRMQ), everyday memory questionnaire (EMQ), digit span test, Beck depression inventory (BDI), and MSQOL questionnaire. Then patients were randomly divided into two groups of treatment (daily regimen of 10 mg donepezil) and placebo for 3 months. Subjects were reassessed using the same instruments at the end of intervention. 

Results:

Fifty patients remained in each group at the end of study. The mean age in donepezil and placebo groups was 31.9 ± 5.89 and 30.65 ± 5.43 years, respectively. EMQ, PRMQ, digit span test, MSQOL, and depression scoresimproved following donepezil therapy (P < 0.001) while no statistically significant difference was found in the placebo group (P > 0.05). Comparison of two groups also showed more favorable scores in donepezil group with respect to all assessment tools (P < 0.001).

Conclusions:

Donepezil could effectively improve cognitive impairment in MS patients. Also, its positive effect on QOL and depression could result in a smaller number of interventions in this group of patients.

Vascular dementia is one of the most common forms of dementia. At now, there is no treatment available to cure vascular dementia or to alter its clinical course. Some studies suggest that some drugs may be useful in controlling symptoms. The aim of this study was to evaluate the effects of donepezil, memantine, rivastigmine and galantamine on mean flow velocity and Mini-Mental State Examination of patients with vascular dementia in a three- month follow-up period.

This double-blind clinical trial was conducted on 44 patients with vascular dementia. Vascular dementia was diagnosed based on the DSM-V criteria. According to the order of entry into the study, the participants were treated with one of the selected drugs [donepezil (10 mg/d), memantine (10 mg/d), galantamine (8 mg/d) and rivastigmine (6 mg/d)]. The sampling finished whenever 11 patients in each group completed the three-month trial. The MMSE and color Doppler ultrasound was performed for all participants before and three months after the intervention.

According to the findings, there was no significant difference among the groups in the frequency of variables and the mean scores of Mini-Mental State Examination before the intervention, but the administration of memantine and donepezil significantly increased Mini-Mental State Examination score (P = 0.009 and P = 0.001 respectively). Moreover, rivastigmine, galantamin and donepezil significantly increased mean flow velocity in some arteries.

Memantine and donepazil improve cognitive function in patients with vascular dementia. Rivastigmine, galantamin and donepezil have some effects on cerebral blood flow.

Cognitive impairment is a common complication of patients with temporal lobe epilepsy (TLE). Therefore, the aim of this study was to compare the effects of donepezil and memantine on improving the cognitive function of patients with TLE.

In a clinical trial study, 70 patients with TLE were divided into two groups of 35 each: 10 mg doses of donepezil (first group) and memantine (second group) were applied for 16 weeks. The level of cognitive function of patients in both groups before and after treatment was determined using Montreal Cognitive Assessment (MoCA) test.

The mean score of MoCA before and after intervention was 23.55 ± 3.67 and 26.09 ± 2.5, respectively, in the group treated with memantine, and the mean score of intervention was significantly improved (P < 0.001). In the group treated with donepezil, the score before and after the operation was 23.87 ± 3.18 and 24.35 ± 2.17, respectively, and no significant difference was observed in this group (P = 0.38).

Hence, memantine was better than donepezil in the improvement of cognitive impairment in patients with TLE.

Alzheimer’s disease (AD) is a degenerative brain disorder and the major cause of dementia and cognitive deficits in the elderly. Riluzole modulates glutamate concentration and improves memory performance in aged rats and may be of benefit in AD. Donepezil is a cholinesterase inhibitor that is used for the treatment of mild-to-moderate AD. In this study, we compared their effects on attenuation of learning and memory deficits in a rat model of AD.

Scopolamine injection for 14 consecutive days induced memory impairment. Effect of riluzole on this impaired memory was evaluated by Morris water maze protocols: accusation phase and probe trial test. Adult male Wistar rats (250–300g) were trained for 4 consecutive days, 24 hours after last scopolamine injection. Spatial memory and learning index (%) were measured depending on the time taken to find the platform and the time utilized in the target quadrant (Q2 ). The time/distance was measured by the computer. Results were analyzed by one-way analysis of variance and Tukey post hoc.

Riluzole was effective in the treatment of memory impairment of scopolamine-injected group. The riluzole-treated group, on test day, showed better spatial memory rather than scopolamine-treated group. Besides, learning index (%) improvement was significantly higher in the riluzole-treated group, rather than scopolamine-injected group.

It can be concluded that riluzole administration at the same time with scopolamine injection or after it causes marked improvements in learning index during training days and the spatial memory on the test day. Therefore, this study strengthens the hypothesis that acute riluzole treatment is capable of treatment of diseases related to memory impairment such as AD

Donepezil (DON), an Acetylcholinesterase Inhibitor (AChEI), is widely used in the treatment of Alzheimer’s Disease (AD). The current study aimed at evaluating the effect of donepezil hydrochloride on pyramidal neuron response in CA1 region of a rat model of AD. In the current experimental study, adult male Wistar rats were randomly divided into four groups: Nucleus Basalis Magnocellularis (NBM) lesion (the lesions were induced by an electrical method of 0.5 m A, for 3 s in NBM) and three donepezil groups (lesions plus 5, 10, and 15 mg/kg donepezil intraperitoneal injection). Neuronal spontaneous activity to injection of the donepezil and saline were recorded in CA1 region of hippocampal. The obtained results showed that IntraPeritoneal (IP) injection of donepezil (10 and 15 mg/kg) increased neuronal spontaneous activity in the rat model of AD. The current study results suggested that acute IP injection of donepezil increased neuronal response in CA1 region of hippocampal in a rat model of AD.