Drug Database
DO

donepezil (E 2022 / TK023 / TK 023)

✓ Approved

Eisai Co., Ltd. · ACHE · Small Molecule

What is donepezil?

donepezil is a small molecule developed by Eisai Co., Ltd.. It is approved for therapeutic indications via transdermal.

Drug Profile

Brand NamesE 2022, TK023, TK 023
CompanyEisai Co., Ltd.
Drug ClassSmall Molecule
Molecular TargetACHE
RouteTransdermal
StatusApproved
Sources: ClinicalTrials.gov, Eisai Co., Ltd.

Mechanism of Action

Molecular Targets

donepezil acts on 1 molecular target:

ACHEacetylcholinesterase (Cartwright blood group) (N-ACHE, ACEE)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

donepezil is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Nervous system disordersDementia Alzheimer's typePhase I

Related Research Articles

PubMedDrug delivery and translational research2026-05-24

Preserving the gut microbiome: hydrogel-forming microneedle delivery of tetracycline reduces gut microbiome disruption compared to oral administration.

Kelly Stephen A SA, Zhao Li L, Nzakizwanayo Jonathan J, Rodgers Aoife M AM et al.

Antibiotics cause significant gut microbiome dysbiosis, particularly when administered orally. This contributes to antimicrobial resistance (AMR) and is associated with myriad health conditions. Novel drug delivery strategies that minimize gut exposure while maintaining therapeutic efficacy are urgently needed. This study aimed to evaluate whether a novel transdermal system could reduce gut microbiome disruption compared to oral delivery. Sprague-Dawley rats received a single tetracycline dose via oral gavage, IV injection, or hydrogel-forming microneedle patch. Faecal samples were collected longitudinally and analysed using 16 S rRNA gene sequencing. Oral tetracycline caused the greatest disruption to gut microbiota. Compared to the timepoint immediately prior to treatment (Day 5a), peak dysbiosis was observed at Day 7. The Firmicutes: Bacteroidetes ratio was significantly reduced following oral and IV tetracycline therapy, but not following microneedle administration. The most significant reductions in alpha and beta diversity at Day 7 were observed in the oral group. Differential abundance analysis showed oral treatment resulted in the highest number of depleted and enriched taxa. The microbiome-sparing effect of microneedle delivery was consistent across all analytical measures, offering a promising strategy to preserve host microbiome health. This minimally invasive approach represents a clinically viable alternative to oral and IV antibiotic administration.

PMID 42177348
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PubMedChemical biology & drug design2026-05-24

Novel Donepezil-Chalcone Hybrids as Potential Multifunctional Anti-Alzheimer's Disease Agents: Design, Synthesis, Computational Simulation, and In Vitro/In Vivo Biological Evaluation.

Lin Zhiqi Z, Jiang Zhenze Z, Chen Die D, Liu Yuanxiu Y et al.

A novel series of donepezil-chalcone including pyridine, piperazine, phenylamide skeleton hybrids were designed, synthesized, and evaluated for their inhibitory activities against AChE and BChE. Subsequently, a subset of these derivatives was investigation to inhibit Aβ1-42 aggregation and promote Aβ1-42 disaggregation effects. Among them, compounds 8b, 8c, 8j, and 8ab possessing good activity were further assayed for their inhibitory effects on BACE-1 and GSK3β, as well as their PI displacement activity. 8b (AChE, IC50: 0.11 μM; BChE, IC50: 0.18 μM; Aβ1-42 aggregation, IC50: 3.40 μM; their ability to promote Aβ1-42 disaggregation, IC50: 4.53 μM; BACE-1, IC50: 1.82 μM; GSK3β, IC50: 0.98 μM) exhibited prominent bioactivities across the above assays. Meanwhile, the molecular docking and the molecular dynamics simulations were performed to analyze the interactions between 8b and the key amino acid residues of the target proteins, which verified the stability of the corresponding protein ligand complexes. Furthermore, 8b significantly attenuated the cytotoxicity induced by Fe3+ and Cu2+ in BV-2 microglial cells, L-Glu in HT-22 hippocampal neuronal cells, and Aβ1-42 in both BV-2 and SH-SY5Y neuroblastoma cells. Additionally, 8b reduced the levels of intracellular ROS and NO in LPS-stimulated BV-2 cells, demonstrating potent anti-inflammatory and neuroprotective properties. Acute toxicity tests in mice confirmed the safety profile of 8b. In in vivo studies, compound 8b effectively protected against neuroinflammation 8b ameliorated cognitive deficits in mice induced by AlCl3 combined with L-galactose, which was associated with the upregulation of p-GSK3β and the downregulation of p-Tau expression. In conclusion, 8b holds great potential as a promising multitarget-directed new lead compound for the treatment of AD.

PMID 42175774
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PubMedScientific reports2026-05-24

Lenalidomide ameliorates cognitive impairment via putative AChE inhibition: an in silico and in vivo study in a scopolamine-induced cognitive impairment model.

Sheikh Salehin S, Shadin Md M, Eity Tanzila Akter TA, Oni Most Israt Jahan MIJ et al.

Alzheimer's disease (AD) causes progressive cognitive decline, and current therapies provide limited benefit. This study evaluated the neuroprotective effects of lenalidomide (LLM), a thalidomide derivative, in a scopolamine-induced mouse model of cognitive impairment, with emphasis on its acetylcholinesterase (AChE) inhibitory potential. Mice received LLM (5, 10, and 20 mg/kg), donepezil (DNP) (3 mg/kg), or a combination and were assessed using Y-maze, passive avoidance, novel object recognition, and Morris water maze tests. In silico analysis, including molecular docking, 100 ns molecular dynamics simulation and ADMET profiling were performed to investigate the interaction of LLM with AChE. Memory performance showed a significant and dose-dependent improvement after the treatment of LLM. The 20 mg/kg dose exhibited effects comparable to DNP. LLM and DNP work together to increase effectiveness. Docking and simulation analyses revealed strong, stable binding to AChE while ADMET values indicated good drug-likeness. LLM exhibits neuroprotective and cognition enhancing effects in the scopolamine-induced model. In silico study also shows its potential as an AChE inhibitor. The study's anti-inflammatory mechanisms might also be helpful but need more exploration.

PMID 42177211
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PubMedBiosensors & bioelectronics2026-05-24

Core-shell inverse opal photonic crystal hydrogel microneedle patch integrating pH and histamine sensing for salmon freshness monitoring.

Qiu Yang Y, Liu Wenzhao W, Zhou Jun J, Wu Zhaoyang Z

Food freshness monitoring remains a significant challenge owing to the complex and diverse nature of spoilage-related biomarkers. Here, we report a core-shell inverse opal photonic crystal hydrogel microneedle patch that enables dual-parameter (pH and histamine) sensing for minimally invasive food freshness assessment. The microneedles are reinforced with a transient polyvinyl alcohol coating to provide sufficient mechanical strength for tissue penetration. This coating rapidly dissolves to expose the sensing hydrogel. The inverse opal structure offers a large specific surface area and facilitates rapid analyte diffusion, enabling fast and sensitive responses. Histamine detection, based on molecular imprinting, achieves a limit of detection of 0.011 mM with a maximum reflection peak shift of 116 nm. The pH-responsive microneedles exhibit a broad detection range (pH 3-10), a maximum wavelength shift of 224 nm, and a rapid response time of 50 s. The sensing signals are readily visualized as structural color changes and quantified via reflection peak shifts. The platform exhibits excellent selectivity and reproducibility. In situ detection in salmon samples shows strong correlation with high-performance liquid chromatography results, confirming its practical applicability. This work presents a versatile microneedle-based platform for real-time, multi-biomarker monitoring of food freshness.

PMID 42176552
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PubMedEuropean journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V2026-05-24

Tuning lipid monolayer behavior with soluble surfactants: A pathway to enhanced ultradeformable drug carriers.

Dopierała Katarzyna K, Przybylska Alicja A, Kustrzyńska Karolina K, Michniak-Kohn Bożena B

Transferosomes are ultradeformable lipid vesicles used to enhance transdermal drug delivery. Their key component is the edge activator, which modulates membrane fluidity and deformability. In this study, we propose an integrated approach to evaluate the surfactants-Tween® 20, Tween® 60, Tween® 80 (Croda International), and sodium cholate (SC)-as edge activators in transferosomal formulations with 1,2-dioleoyl-3-trimethylammonium propane (DOTAP). Monolayer and bilayer investigations were combined to identify the most suitable surfactant. Among the investigated surfactants, SC exhibited the most favorable overall performance, leading to transferosomes with enhanced membrane fluidity and desirable viscoelastic properties. The results also revealed a strong influence of surfactant concentration on the interfacial behavior of the lipid bilayer, attributed to electrostatic interactions between SC and DOTAP. Atomic force microscopy confirmed increased vesicle deformability from 4.10 to 8.83 nm and reduced Young's modulus from 167.29 to 88.22 MPa for SC-containing systems compared to pure DOTAP. DLS measurements further demonstrated appropriate colloidal properties, with vesicle size of 216-345 nm. Within a simplified Quality by Design framework, SC emerged as the most promising edge activator, although adhesion-related parameters did not clearly indicate dominance of this formulation. Overall, the proposed integrated strategy provides a rational approach for the rational design of transferosomal formulations.

PMID 42176870
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PubMedEndocrine2026-05-24

Fractionated testosterone gel replacement therapy in clinical practice: A real-world exploratory clinical experience.

Maltese Virginia V, Delbarba Andrea A, Gatta Elisa E, Vetrugno Simone S et al.

Testosterone replacement therapy (TRT) with transdermal gel is widely used in men with hypogonadism. Guidelines recommend once-daily application with monitoring of serum testosterone at peak levels. However, real-world clinical experience suggests that peak-trough fluctuations in some patients, potentially affecting hormonal stability and treatment tolerability. The impact of dose fractionation remains unclear. To compare hormonal profiles and biochemical safety parameters between once-daily and twice-daily (fractionated) testosterone gel administration in hypogonadal men receivingh the same total daily dose. We retrospectively identified hypogonadal men treated with 2% testosterone gel who transitioned from once-daily to twice-daily dosing, maintaining the same total daily dose. Eligible patients had serum total testosterone (TT) measurements available at both peak (3 h post-application) and nadir (pre-dose). Hormonal and laboratory parameters under the two regimens were compared. Twelve patients met inclusion criteria. Fractionated dosing was associated with lower peak TT levels [9.0 (5.3-13.0) vs. 5.7 (3.6-7.1) ng/mL, paired difference - 3.6 ng/mL (95% CI: -4.9 to - 1.8)] and higher nadir TT levels [1.4 (1.1-1.8) vs. 3.2 (2.6-5.4) ng/mL, paired difference 2.6 ng/mL (95% CI: 1.2 to 5.1)], resulting in a reduced difference between peak-to-pre-dose difference within the observed sampling window. The proportion of patients achieving target TT levels at peak increased (33% vs. 83%). Calculated free testosterone showed a similar pattern. No clinically relevant differences were observed in luteinizing hormone, prostate-specific antigen, haematocrit, or haemoglobin. In this real-world cohort, fractionated testosterone gel administration was associated with a higher proportion of patients achieving biochemical targets and with a reduced peak-to-pre-dose difference within the observed sampling window, without short-term biochemical safety signals. These findings should be considered hypothesis-generating.

PMID 42176213
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