donepezil / Generic mfg. - LARVOL DELTA

Targeting cholinergic dysfunction and neuroinflammation through rationally designed Thieno[3,2-d]pyrimidine hybrids. (PubMed, Bioorg Chem) - "Among them, compounds 5 and 9 emerged as the most active derivatives, displaying Ki values of 8.79 and 14.11 nM for AChE and 7.04 and 11.75 nM for BChE, surpassing the reference inhibitors tacrine and donepezil. This integrated enzymatic, computational, and cellular investigation identifies compounds 5 and 9 as promising multifunctional lead combining dual cholinesterase inhibition with robust anti-neuroinflammatory activity. The results provide a strong foundation for future in vivo studies and further optimization toward disease-modifying agents for neurodegenerative disorders."

Journal • CNS Disorders • Inflammation • Pain • IL1B • IL6

ASSESSMENT OF ORTHOSTATIC TOLERANCE AND EFFICACY OF FIMASARTAN IN ELDERLY ALZHEIMER'S DISEASE PATIENTS WITH HYPERTENSION: A 16-WEEK OBSERVATIONAL STUDY (ADPD 2026) - "Aims: This study aimed to evaluate the effects of the Korean Angiotensin II receptor Block(ARB), Fimasartan on BP control, orthostatic stability, and cognitive function in hypertensive eAD patients, with a focus on safety and tolerability. A total of 35 participants with hypertension and eAD were included, All patients were met the NIA-AA Criteria on a stable dose of donepezil medication for at least 4weeks prior to the study. Fimasartan effectively reduced BP in hypertensive eAD patients without worsening autonomic symptoms such as OH or dizziness. The medication was well tolerated, with no significant impact on cognitive function or new safety concerns. This suggest that Fimasartan may be a safe and viable option for managing hypertension in patients with eAD."

Clinical • Observational data • Alzheimer's Disease • Cardiovascular • CNS Disorders • Hypertension

DISCOVERY OF NOVEL ALPHA-KETOAMIDE DERIVATIVES AS DUAL AMYLOID-BETA AND TAU AGGREGATION MODULATORS FOR ALZHEIMER'S DISEASE THERAPY (ADPD 2026) - "MD08 exhibits dual inhibitory activity against amyloid beta and tau aggregation, along with good solubility, blood–brain barrier permeability, in vitro safety, and dose-dependent cognitive improvement in vivo, underscoring its potential as a promising therapeutic lead for Alzheimer's disease"

Alzheimer's Disease • CNS Disorders

FLAVONOIDS-RICH EXTRACT FROM BACOPA FLORIBUNDA AMELIORATES AMYLOIDOGENESIS IN AΒ1-42 MODEL OF ALZHEIMER'S DISEASE IN BALB/C MICE (ADPD 2026) - "Groups 1-3 represent the normal, sham and negative controls, while groups 4-7 received donepezil, FBF at 50mg/kg, 100mg/kg and 200mg/kg respectively for 21 days... In conclusion, FBF could be effective in alleviating the direct toxic effects of Aβ1-42 thereby disrupting its mechanisms of actions leading to Alzheimer's disease progression."

Preclinical • Alzheimer's Disease • Behavior Disorders • CNS Disorders • Dementia • Dyslipidemia • Mental Retardation • Metabolic Disorders • BDNF

REVERSAL OF BIPERIDEN-INDUCED COGNITIVE IMPAIRMENT BY DONEPEZIL: A PROOF-OF-PHARMACOLOGY TOOL FOR MUSCARINIC MODULATORS IN HEALTHY ELDERLY (ADPD 2026) - "The model demonstrated low and acceptable intersubject (∼30–35%) and intrasubject (∼18–24%) variability in plasma Cmax and AUC0–last, further supporting its reliability for repeated-measures study designs. These findings validate the 2.6 mg IV biperiden challenge model as a robust tool for proof-of-pharmacology studies of novel mAChR modulators in early-stage clinical development."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

BLOOD BIOMARKERS, MRI, AND EEG FINDINGS IN PSEN1 L392V MUTATION: CASE REPORT (ADPD 2026) - "He was started on Donepezil... This case highlights the rapidly progressive features of PSEN1 L392V, evidenced by elevated p-tau levels, marked atrophy, and seizures."

Biomarker • Case report • Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Epilepsy • Aβ42 • p-tau181

BLOOD-BASED BIOMARKERS IN ALZHEIMER'S DISEASE: CORRELATION ANALYSIS, LONGITUDINAL TRENDS, AND THE EFFECTS OF DONEPEZIL (ADPD 2026) - "Higher tau levels relate to worse and higher Abeta 42/40 ratio to better cognition. Both p-tau181 and p-tau217 showed an increasing trend over time, whereas Abeta42/40 ratio showed a decreasing trend, supporting the underlying pathology. No statistically significant correlations between MMSE and any BBM were observed at individual time points, though the direction of changes aligned with disease progression."

Biomarker • Alzheimer's Disease • CNS Disorders • Aβ42 • p-tau181

Donepezil for Korsakoff Syndrome. (PubMed, Am J Ther) - "The off-label use of donepezil for Korsakoff syndrome in this case and others has been shown to be beneficial and well tolerated. Ultimately, larger studies are needed to determine safety and efficacy."

Journal • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders

Efficacy and safety of Woohwangchungsimwon in combination with donepezil for behavioral and psychological symptoms of dementia in probable Alzheimer's disease: An assessor-blinded randomized controlled trial. (PubMed, J Alzheimers Dis) - "No significant differences in adverse events or laboratory results were observed.ConclusionsWCW may be a safe and effective adjunctive therapy for BPSD in patients with mild probable AD. Future studies should adopt more rigorous designs and include patients with broader disease severity to enhance clinical applicability.Trial registrationThe trial was registered with the Clinical Research Information Service (CRIS) on December 10, 2020 (KCT0005669)."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Depression • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder

Differential effects of cariprazine, LY379268 and donepezil on EEG oscillations and auditory steady-state response in MK-801-treated rats: relevance for schizophrenia drug development. (PubMed, Neuropharmacology) - "These results highlight shed new lights on potential pharmacological strategies focused on circuits dysfunction andsymptoms in SZ. These differential normalization profiles, including cariprazine's unique broad-spectrum signature, reveal distinct patterns of circuit engagement and provide a translational pharmaco-EEG framework for circuit-level target engagement in SZ drug development."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

New benzimidazole-alkanesulfonate conjugates as cholinesterase inhibitors with in vitro and in silico validation. (PubMed, Sci Rep) - "The antioxidant potency (represented by TAC and IRP) and scavenging activity (represented by DPPH, ABTS, NO, OH, and H2O2) revealed that compounds 4q and 4r possess remarkable antioxidant potential, comparable to the reference antioxidant ascorbic acid. Furthermore, in silico ADME prediction and molecular docking studies were performed to predict their binding modes and interactions in the AChE binding pocket; the results revealed that derivatives 4q and 4r showed the highest binding affinity among the tested series and the reference drug donepezil, which validated the obtained in vitro results."

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

Whiteness and greenness metric tools for assessment of the spectrophotometric methods sustainability: mathematical manipulation of absorption spectra to resolve the interfering donepezil HCl and pentoxifylline in ethoniosomes. (PubMed, BMC Chem) - "Validation of the suggested methods has been carried out in accordance with ICH standards with regard to linearity, detection limit, quantification limit, precision, and accuracy. The evaluation of whiteness, blueness, and greenness measures confirmed that the recommended strategies show a significant advantage over previously published ones."

Journal

The impact of slope-adjusted visit-to-visit body mass index variability on early dementia risk prediction. (PubMed, Int J Obes (Lond)) - "Slope-adjusted visit-to-visit BMI variability is independently associated with dementia risk, particularly among females, while BMI decline patterns are strong risk factors of dementia. Incorporating longitudinal monitoring of visit-to-visit BMI variability into routine dementia screening may be beneficial."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

Danggui Shaoyao San ameliorates neuroinflammation in a D-galactose-induced Alzheimer's disease rat model by suppressing the JAK2/STAT3 pathway and modulating Th17/Treg -related immune dysregulation. (PubMed, Front Cell Dev Biol) - "Forty male Sprague-Dawley rats were randomly divided into five groups: control, AD model, low-dose DSS (12 g/kg/day, raw herbal materials), high-dose DSS (24 g/kg/day, raw herbal materials), and donepezil (0.5 mg/kg/day)...Network pharmacology and experimental validation indicated that DSS exerts its anti-neuroinflammatory effects by inhibiting JAK2 and STAT3 phosphorylation, reducing their nuclear translocation, and consequently suppressing Th17 differentiation and pro-inflammatory cytokine production. DSS is a promising candidate for AD treatment, with neuroprotective and cognitive-enhancing properties mediated through immunomodulation and JAK2/STAT3 pathway inhibition."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • Metabolic Disorders

Shenzao Jiannao Oral Liquid treats Alzheimer's disease by regulating gut microbiota (PubMed, Zhongguo Zhong Yao Za Zhi) - "APP/PS1 double transgenic mice were used to establish the AD model and then allocated into the following groups: model(normal saline of equal volume), positive drug(donepezil hydrochloride, 0.65 mg·kg~(-1)), and low-, medium-, and high-dose(0.3, 1.5, and 7.5 g·kg~(-1), respectively) SZJN...Gut microbiota analysis revealed increased species diversity and richness in the high-dose SZJN groups, with microbiota structures resembling that in the blank group. These results confirm that high-dose SZJN improves the learning and memory abilities, mitigates intestinal pathological damage, and protects the intestinal tissue of AD mice by regulating the gut microbiota."

Journal • Alzheimer's Disease • CNS Disorders • OCLN • TJP1

Ultraweak Photon Emission as a Noninvasive Biomarker of Neural Metabolism: A Narrative Review of Emerging Evidence (AAN 2026) - "In neurodegenerative models, baseline UPE is reduced, and glutamate-evoked responses show diminished amplitude and spectral blue shift, consistent with impaired mitochondrial and synaptic activity. Pharmacologic agents such as donepezil restore UPE profiles toward baseline... Emerging evidence supports UPE as a sensitive, noninvasive optical marker of neural oxidative metabolism. Its responsiveness to disease state and pharmacologic modulation warrants further translational studies to establish diagnostic thresholds and explore integration with EEG, fMRI, and metabolic imaging in clinical neurology."

Biomarker • Non-invasive • Review • Cardiovascular • CNS Disorders • Epilepsy • Ischemic stroke

Integrated computational, pharmacological and molecular investigations of piperitone in mitigating Alzheimer disease pathology by targeting cholinesterases, β-secretase and neuroinflammation. (PubMed, Inflammopharmacology) - "In-vivo assessment of spatial memory in scopolamine-induced rat model was identified by behavioral assays with donepezil as a reference standard...Piperitone demonstrated favorable PK properties & docking scores comparable to Donepezil, Tacrine & QUD...Piperitone showed significant neuroprotective and cognitive enhancement benefits by modulating cholinergic signaling, oxidative stress, and neuroinflammation. These multitarget actions advocate piperitone as a prospective lead candidate for the development of disease modifying treatments for AD."

Journal • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Inflammation • Oncology • Pain • CAT • IL18 • NLRP3 • TNFA

Normal serum cholinesterase does not exclude donepezil or galantamine toxicity: an interpretive pitfall of BuChE-based testing. (PubMed, Clin Biochem) - "Potential explanations include limited BuChE inhibition by these agents and assay-related underestimation of reversible AChE inhibition under dilutional conditions. Normal serum cholinesterase should therefore not be used to rule out donepezil or galantamine toxicity; clearer test labeling as BuChE activity may reduce misinterpretation."

Journal • Pain

Machine Learning-Integrated Pharmacophore, DFT Analysis, and molecular dynamics of Diosmetin as a potent ache inhibitor with neuroprotective activity in a Scopolamine-Induced alzheimer's zebrafish model. (PubMed, J Comput Aided Mol Des) - "Biochemistry revealed that diosmetin counteracted the scopolamine-induced increase in AChE activity, increased oxidative stress, increased myeloperoxidase inflammatory markers, decreased antioxidant activity, and restored normal histology in the brains of the zebrafish. Most importantly, high-dose diosmetin demonstrated comparable neuroprotective efficacy to donepezil in behavioral and biochemical assays while exhibiting weaker molecular binding affinity toward AChE, as indicated by MM-PBSA analysis, underscoring that similar in vivo outcomes do not necessarily imply molecular equivalence at the binding level."

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

Investigating the Cholinergic Contribution to Gait Dysfunction in Parkinson's Disease (clinicaltrials.gov) - P2 | N=6 | Completed | Sponsor: University of Virginia | Recruiting ➔ Completed | Trial completion date: Sep 2025 ➔ Jan 2026

Trial completion • Trial completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Therapeutic relevance of an EU-GMP certified Cannabis sativa L. strain in a dual in vivo model of cognitive impairment and chronic neuropathic pain. (PubMed, Front Pharmacol) - "The study evaluated the effects of an EU-GMP certified Cannabis sativa L. strain (5 mg/kg, Cannabixir® Medium Flos) on neurobiological alterations in a rat model designed to explore mechanistic interactions between scopolamine-induced transient cognitive impairment and chronic neuropathic pain induced by unilateral sciatic nerve ligation...Cannabixir® Medium Flos induced robust, time-dependent analgesia in thermal nociceptive tests, with the combination of the Cannabis sativa L. strain, donepezil and tramadol producing significantly longer response latencies than tramadol alone...Its multi-target action - alleviating thermal nociception, reducing neuroinflammation, limiting apoptosis and preserving neuronal and peripheral nerve integrity-supports its potential as an adjunct therapy in managing dementia with comorbid chronic neuropathic pain. Future studies should explore the molecular mechanisms underlying these effects and assess long-term safety and..."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • Neuralgia • Pain • CASP3 • GFAP • IL6

Synthesis, spectral characterization, and cholinesterase inhibitory evaluation of benzothiazole-linked oxadiazole derivatives as potential anti-Alzheimer's agents. (PubMed, Bioorg Chem) - "All derivatives were evaluated for their cholinesterase inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with donepezil used as the reference drug...Molecular docking studies supported the experimental results, revealing strong binding interactions of K2 and K7 with AChE and BChE, respectively. In silico ADME analysis indicated favorable drug-like properties for all compounds, suggesting their potential as promising leads for Alzheimer's disease therapy."

Journal • Alzheimer's Disease • CNS Disorders • Pain

Design, Synthesis, In Vitro and In Vivo Biological Evaluation of Novel Pyrazolo[3,4-d]Pyrimidine-Based Derivatives as Promising Multitarget Candidates for Alzheimer's Disease. (PubMed, Drug Dev Res) - "Compound 8b (IC50 = 0.346 μM) and 9a (IC50 = 0.168 μM) are the most potent inhibitors of AChE relative to donepezil (IC50 = 0.213 μM)...The in vivo investigation of the most potent compounds (8b and 9a) revealed a significant improvement in scopolamine-induced cognitive deficits in animals...Finally, In silico physicochemical and pharmacokinetics prediction analyses were performed, and the findings were well aligned with their corresponding in vitro results. Overall, the results highlight 8b and 9a as potential multifunctional candidates for AD."

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

Effect of DL0410 and tetrahydrocurcumin (LG0367) alone and in combination on learning and memory in vascular dementia. (PubMed, Eur J Pharmacol) - "Here, using bilateral common carotid artery occlusion (2VO) rat model, we found that the combined treatment of DL0410 and LG0367 had a much better effect on improving cognitive function in rats than single-drug treatment or donepezil, suggesting a synergistic effect between the small-molecule drug DL0410 and the natural derivertive LG0367...Our findings not only demonstrated a potent synergistic effect between the synthetic small-molecule DL0410 and the natural derivative LG0367, but also illuminate a promising "symptom-to-root" therapeutic strategy for VaD, providing a systematic and evidence-based model for modernizing phytotherapy. Ultimately, this study will provide important information for future clinical trials aimed at translating this synergistic combination into a tangible "multi-target, multi-mechanism" treatment option for VaD patients."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Inflammation • Pain • SHH

Hyperforin Attenuates Scopolamine Induced Alzheimer's Pathology in Rat Model: Abrogation of Caspase-1/11 Mediated Pyroptosis via Inhibition of HMGB1-Mediated RAGE Pathway. (PubMed, J Biochem Mol Toxicol) - "Sprague-Dawley rats were divided into four groups: control (saline), scopolamine (10 mg/kg, i.p.), scopolamine + hyperforin (10 mg/kg, p.o. for 7 days), and scopolamine + donepezil. In addition, HPF reduced Aβ formation by downregulating BACE1 and blocking the activity of inflammasomes composed of canonical and non-canonical caspase-1/11. HPF appears to be a potential therapeutic candidate for neurodegeneration associated with AD, given that hyperforin actively demonstrated neuroprotective effects in a scopolamine-induced AD model, most likely through blocking the HMGB1/RAGE signaling pathway, mitigating neuroinflammation and pyroptosis, and inhibiting Aβ synthesis."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Inflammation • BACE1 • HMGB1 • IL18 • IL1B