donepezil / Generic mfg. - LARVOL DELTA

Treatment of apathy in stroke patients: a systematic review. (PubMed, Front Neurol) - "Pharmacological interventions with escitalopram and donepezil (alone or combined with intensive language action therapy) showed potential benefits. Nefiracetam yielded mixed results depending on dose and coexisting depression...Nevertheless, evidence remains scarce and heterogeneous, underscoring the need for larger, high-quality randomized controlled trials to establish definitive treatment guidelines. https://www.crd.york.ac.uk/PROSPERO/view/CRD42022332559."

Clinical • Journal • Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Depression • Hematological Disorders • Psychiatry

Creatine and Taurine as Novel Competitive Inhibitors of Acetylcholinesterase: A Biochemical Basis for Nutritional Modulation of Brain Function. (PubMed, Int J Mol Sci) - "While clinically approved AChE inhibitors such as donepezil, rivastigmine, and galantamine are used in the symptomatic treatment of Alzheimer's disease and related dementias, little is known about the modulatory effects of common dietary compounds on AChE activity. Docking confirmed that both ligands preferentially occupy the active-site region in a manner consistent with competitive inhibition, with CR showing more favorable binding scores than TA. Although markedly weaker than clinical drugs, these findings provide the first biochemical and in silico evidence that CR and TA directly interact with AChE, suggesting subtle cholinergic modulation relevant to cognitive function and neuroprotection."

Journal • CNS Disorders • Dementia • Pain

Molecular Modeling and Analysis of Cannabinoid and Cannabinoid-like Molecules Combining K-Means Clustering with Pearson Correlation and PCA. (PubMed, Int J Mol Sci) - "Additionally, these analogues clustered with classical acetylcholinesterase inhibitors such as huprine-X, huprine-W, and donepezil when considering ADMET and electronic descriptor data. Radulanin J showed the highest correlation (0.41) with donepezil's profile, suggesting the potential of cannabinoid-derived compounds as acetylcholinesterase inhibitors."

Journal • Alzheimer's Disease • CNS Disorders

Behçet Disease and Cognitive Impairment: A Case Study of an Overlooked Symptom. (PubMed, Am J Case Rep) - "She received donepezil, folic acid, cognitive stimulation, and immunosuppressive therapy...CONCLUSIONS This case shows that cognitive impairment can present as an isolated manifestation of BD, even in the absence of overt neurological symptoms. Early neuropsychological screening and timely intervention can prevent progression and preserve quality of life."

Journal • Cardiovascular • CNS Disorders • Cognitive Disorders • Endocrine Disorders • Solid Tumor • Thymoma • Thymus Cancer • Vasculitis

Bioaccumulation of Psychoactive Contaminants and Their Effects on Brain-Gonad-Sperm Neurotransmitter Networks in Fish. (PubMed, Environ Sci Technol) - "Here, we investigated the effects of environmentally relevant concentrations of a mixture of seven PSYCs (citalopram, donepezil, gabapentin, methamphetamine, sertraline, tramadol, and venlafaxine) on European perch (Perca fluviatilis) during a 23 day exposure. No significant changes were observed in gonadal histopathology or sperm-quality parameters; however, the observed molecular alterations suggest potential consequences under longer or chronic exposures. These findings identify sperm as a previously overlooked target for psychoactive pollutants and reveal neurochemical disruption along the brain-gonad-sperm axis as a previously unrecognized mechanism through which PSYCs may affect fish physiology."

Journal

Pterostilbene mitigates scopolamine-induced cognitive impairment by modulating cholinergic pathway and reducing neuroinflammation. (PubMed, Phytomedicine) - "Our findings establish Pte as a novel dual-target therapeutic agent that simultaneously modulates cholinergic function and directly inhibits NLRP3-mediated pyroptosis. The MCC950 competition assay provides evidence of Pte's NLRP3-targeting specificity, offering a promising multi-target alternative to conventional single-pathway treatments for cognitive impairment."

Journal • Cognitive Disorders • Inflammation • NLRP3

Integrative bioinformatics analysis of APOE variants in Alzheimer's disease and clinical therapeutics. (PubMed, J Biomol Struct Dyn) - "However, these computational predictions require validation through biophysical assays, cellular experiments, and genotype-stratified clinical studies. Integrating molecular modeling with experimental research will be essential for advancing APOE-guided precision medicine and optimizing Donepezil therapy for Alzheimer's disease."

Journal • Alzheimer's Disease • CNS Disorders • APOE

Phytochemical profiling and cognitive enhancement effects of Astragalus peregrinus extract and its nanostructured lipid carrier in a D-galactose-induced aging rat model. (PubMed, Nat Prod Res) - "Crude extract and AP-NLCs potential to prevent and treat D-galactose-induced brain ageing in rats was further investigated compared to Donepezil as a standard drug...Additionally, they promoted significant histopathological recovery. The results support using A. peregrinus nano-formulation intranasally, especially when administered prophylactically, to alleviate brain ageing."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Mental Retardation

Synthesis, biological evaluation, and in silico studies of pyridoxal-amiridine hybrids as multitargeting anti-Alzheimer's disease agents. (PubMed, Eur J Med Chem) - "Conjugates were mixed-type reversible inhibitors of AChE and BChE and displaced propidium from the AChE peripheral anionic site at the level of donepezil...Additionally, conjugates demonstrated neuroprotection in models of hydrogen peroxide and glutamate-induced oxidative stress in neuroblastoma SH-SY5Y cells, where compounds 4a,b were more active than 3a,b. Altogether, the results indicated that the new conjugates possessed potential for further development as multifunctional anti-AD drug candidates."

Journal • Alzheimer's Disease • CNS Disorders • Neuroblastoma • Oncology • Pain • Solid Tumor • Aβ42

Repurposing of Cefotaxime for Its Therapeutic Potential in Alzheimer's Disease: An Explanation of the Possible Mechanism of Action. (PubMed, ACS Chem Neurosci) - "Adult male Sprague-Dawley rats were administered CTX (100-300 mg/kg, intraperitoneal, 28 days) and compared with donepezil (5 mg/kg). While CTX reduced mRNA expression of β-amyloid and tau, it did not lower their protein levels as determined by ELISA, suggesting selective modulation at transcriptional rather than post-translational levels. Together, these findings suggest a potential role for CTX as a promising repurposed candidate for alleviating AD-related neurobehavioral deficits through the modulation of oxidative stress and inflammatory pathways."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Inflammation • Mood Disorders • Psychiatry

sc4D: spatio-temporal single-cell transcriptomics analysis through embedded optimal transport identifies joint glial response to Alzheimer's disease pathology. (PubMed, bioRxiv) - "In silico perturbations predict the restoration of protective, anti-inflammatory microglia through CAMTA1 activation or Donepezil, as validated by independent experimental findings. Overall, our work highlights the critical benefits of joint spatio-temporal modeling for elucidating disease mechanisms and predicting candidate interventions to improve cellular response."

Journal • Alzheimer's Disease • CNS Disorders • CAMTA1

Introduction of Cistanche phelypaea fatty acids as a new natural neurotrophic supplement by evaluating its effects in normal and Alzheimer's diseased rats. (PubMed, Sci Rep) - "The study was conducted in two parallel arms, the first arm investigated the effect of C. phelypaea FAs on normal rats, and the second arm investigated its effect on Alzheimer's disease rats and involved the following groups of rats: normal & untreated AD groups, reference group: donepezil (0.75 mg/kg), & C. phelypaea groups (100 and 200 mg/kg), all treatments were given concomitantly with AlCl3 (172.5 mg/kg) to rats, by oral gavage for 3 successive weeks, followed by alternating Y-maze & grid floor activity cage tests, then the levels of acetylcholine esterase (AchE), β-amyloid and tau protein were measured in rats' sera of rats...C. phelypaea FAs had promising effects on brain health."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Pain

Nose-to-Brain Delivery of Donepezil Hydrochloride via Oleic Acid-Conjugated PAMAM G4 Dendrimers for the Treatment of Alzheimer's-Like Dementia. (PubMed, Mol Pharm) - "Neurobehavior studies in male SD rats suggested significant attenuation of AlCl3-induced cognitive decline in DPZ-OA-G4 treated animals, which was further confirmed with biochemical and histological evaluations. In conclusion, this study provides proof of concept that DPZ can be successfully targeted to the brain using ligand-conjugated dendrimeric systems via intranasal administration, a noninvasive route that enables direct nose-to-brain delivery, bypasses the blood-brain barrier, and minimizes systemic side effects."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Pain

Modulation of experimental Alzheimer's disease in rats through donepezil-loaded CSF implant. (PubMed, Sci Rep) - "Histological examination revealed the neuronal regeneration after donepezil-loaded PMMA coated membrane. These findings suggest that coated nanoporous membranes are promising systems for localized active donepezil drug delivery for AD-like symptoms modulation in STZ-induced AD model, warranting further validation in other AD paradigms."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • BDNF

Cognitive stimulation exerts long-lasting protective effects on the hippocampal vasculature and memory function in a rat model of vascular cognitive impairment. (PubMed, NPJ Aging) - "Donepezil improved HA function and rescued memory in isolated, aged SHR. Intermittent cognitive stimulation exerted long-lasting protection on the hippocampus and its vasculature, highlighting the therapeutic potential of HAs and cognitive stimulation in VCI."

Journal • Preclinical • Alzheimer's Disease • Cognitive Disorders • BDNF

Riboflavin-sensitized photoinduced degradation of donepezil hydrochloride: kinetic and computational insights for pharmaceutical formulation. (PubMed, RSC Adv) - "The two-component spectrometric and HPLC green methods have been developed and validated for estimating DPZ and RF in pure and degraded solutions. Additionally, computational studies have been conducted to assess the formation of the ground-state complex, binding affinity, and molecular interactions between DPZ and RF."

Journal • CNS Disorders • Movement Disorders

Lactobacillus gasseri MG4247 and Lacticaseibacillus rhamnosus MG4644 alleviate LPS-induced cognitive impairment via activation of the Akt/CREB/BDNF signaling pathway. (PubMed, Behav Brain Res) - "These improvements were comparable to LPS model mice cotreated with the clinical acetylcholinesterase inhibitor donepezil...These findings suggest that L. gasseri MG4247 and L. rhamnosus MG4644 mitigate LPS-induced cognitive deficits through anti-inflammatory effects and activation of the Akt/CREB/BDNF pathway. This study supports the potential of probiotics for suppressing neuroinflammation and enhancing cognitive function via neural, immune, and endocrine pathways of the gut-brain axis."

Journal • CNS Disorders • Cognitive Disorders • Inflammation • IL6 • TNFA

Hybrid molecules with dual inhibition of acetylcholinesterase and Tau hyperphosphorylation: design, inhibitory activity evaluation, apoptosis assessment, and mechanistic exploration. (PubMed, Chem Biol Interact) - "To address this need, the present study designed a series of hybrid molecules by integrating three pharmacophoric scaffolds with established P-Tau-modulating activity (phenothiazine, dibenzazepine and benzothiazepinones) into AChE-inhibiting frameworks: indanone (derived from the clinical AChE inhibitor Donepezil) or 9-chloro-1,2,3,4-tetrahydroacridine (derived from Tacrine, another clinically approved AChE inhibitor)...Notably, the indanone-phenothiazine hybrid compound C11 stood out as the most promising candidate, it achieved the lowest P-Tau/total Tau (T-Tau) ratio (5.30 × 10-6) in okadaic acid (OA)-induced SH-SY5Y cells, outperforming hydromethylthionine mesylate (5.40 × 10-6), a leading clinical candidate for Tau aggregation inhibition...Concurrently, C11 modulated the expression of glycogen synthase kinase-3β (GSK-3β), a critical kinase driving P-Tau formation."

Journal • CNS Disorders

Administration of Cilostazol Mitigates Learning and Memory Disturbance in a Rat Model of Amnesia by Modifying Cholinergic Function and Neuroinflammation. (PubMed, Mol Neurobiol) - "To investigate the neuroprotective mechanisms of Cil, oral treatment with Cil and donepezil (DNP, positive control) was administered over three weeks. Additionally, Cil and DNP elevated hippocampal levels of sulfhydryl groups (P = 0.01-P"

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Inflammation • CHRM1 • IL1B • TNFA

Donepezil treatment, alone or combined with exercise, enhances skeletal muscle function in healthy and advanced aging disease mouse models. (PubMed, J Appl Physiol (1985)) - "However, cholinesterase inhibition had minimal effects in a model of advanced aging. Further research is needed to determine if cholinesterase inhibitors can combat age-related muscle decline."

Journal • Preclinical • CNS Disorders

Comparative Effectiveness of Interventions to Treat Cancer Treatment-Related Cognitive Impairment in Adult Cancer Survivors Following Systemic Therapy: A Systematic Review with Network Meta-Analyses. (PubMed, Cancers (Basel)) - "While findings suggest that structured multimodal group interventions may represent the most promising strategy for CTRCI, CoE was low, and additional rigorous, standardized trials are required."

HEOR • Journal • Review • Brain Cancer • CNS Tumor • Cognitive Disorders • Oncology

A novel multimodal pharmacologic approach using guanfacine, N-acetylcysteine, and donepezil in severe TBI: a case series. (PubMed, Front Rehabil Sci) - "The encouraging outcomes observed in this case series underscore the potential of the GND regimen as a multimodal pharmacologic approach to target the complex neurochemical disruptions following TBI. These preliminary findings warrant further investigation in larger, placebo-controlled trials in order to more rigorously assess the safety, efficacy, and translational potential of this intervention for mitigating chronic cognitive sequelae in individuals with moderate to severe TBI."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Dementia • Vascular Neurology

The imperative for multigenerational genetic screening: A case report of fragile X-associated tremor/ataxia syndrome (FXTAS). (PubMed, Medicine (Baltimore)) - "Due to the highly variable clinical presentation of FXS within families, clinicians should always consider fragile X testing and detailed family history when middle-aged and elderly males exhibit unexplained cognitive impairment or tremors. With the acceleration of aging in society, this case underscores the importance of multigenerational genetic screening for maternal grandparents, particularly males, in FXS families and prioritizing follow-up monitoring."

Journal • Ataxia • Cognitive Disorders • Fragile X Syndrome • Movement Disorders • FMR1

Comparative effects of respiratory stimulants in mechanically ventilated patients: a network meta-analysis of randomized controlled trials. (PubMed, Sci Rep) - "A systematic search of PubMed, Web of Science, and Scopus (up to November 10, 2023) identified 15 randomized controlled trials (1,528 participants) evaluating ten respiratory stimulants in mechanically ventilated critically ill adults: Almitrine Bismesylate (AB), Doxofylline (DX), Progesterone (PRG), Acetazolamide (ACZT), Growth Hormone (GH), Oxandrolone (OXA), Nandrolone (NA), Caffeine (CAF), Donepezil (DPZ), and a multi-agent adjuvant therapeutic (AT) regimen containing anisodamine. However, agents such as NA, GH, and DPZ may help shorten ICU stay, reduce duration of mechanical ventilation, or improve weaning efficiency. These findings underscore the potential value of multi-agent adjuvant approaches and highlight the need for larger, high-quality trials to confirm their clinical benefits.Trial registration: CRD42023454122 (18/10/2023)."

Journal • Retrospective data • Critical care

Investigation of 2-substituted-5-methylsulfonylbenzoxazole derivatives as potential cholinesterase inhibitors: Synthesis, in vitro, and computational studies. (PubMed, Bioorg Chem) - "Accordingly, all compounds except C1, C2, C11, and C12 were found to be more effective than donepezil against AChE, and all compounds except C1, C5, and C12 were found to be more effective than donepezil against BChE...Additionally, the molecular electrostatic potential (MEP) map of all compounds and the extent to which the HOMO-LUMO energy gaps affect the reactivity, stability, and inhibitor profiles of these compounds were investigated using density functional theory (DFT) studies, a computational analysis method. The study proves that 2-substituted-5-methylsulfonylbenzoxazole derivatives exhibit potent and selective cholinesterase inhibition."

Journal • Preclinical • Pain