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donepezil (IPI301 / donepezil, iCure / Donerion)

✓ Approved

Icure Pharmaceutical Incorporation · ACHE · 小分子

什么是 donepezil？

donepezil 是一种小分子，由Icure Pharmaceutical Incorporation研发。该药已获批，用于治疗相关适应症，给药途径：Transdermal。

药物档案

商品名IPI301, donepezil, iCure, Donerion
公司Icure Pharmaceutical Incorporation
药物类别小分子
分子靶点ACHE
给药途径Transdermal
状态Approved
来源： ClinicalTrials.gov, Icure Pharmaceutical Incorporation

作用机制

分子靶点

donepezil 作用于 1 个分子靶点：

ACHEacetylcholinesterase (Cartwright blood group) (N-ACHE, ACEE)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

donepezil 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Nervous system disordersDementia Alzheimer's type✓ Approved

相关研究文献

PubMedChemMedChem2026-06-11

Synthesis and Evaluation of Novel Cinnamic Acid Hybrids With Antiacetylcholinesterase, Antioxidant, and Anti-Inflammatory Properties.

Sdougkou Konstantina K, Rekka Eleni E, Papagiannopoulou Dionysia D

Alzheimer's disease, one of the most widespread neurodegenerative disorders, is known for its multifactorial nature that makes it challenging to treat. In the present work, hybrid molecules were designed and synthesized combining the anti-acetylcholinesterase (AChE) activity of donepezil with the antioxidant and/or anti-inflammatory activity of selected cinnamic acids. In particular, the new derivatives were conjugated by Steglich esterification or amidation of suitable benzylpiperazine/piperidine moieties with ferulic, sinapic, 3,4-dimethoxycinnamic acids. All new molecules were evaluated for their activity in terms of AChE inhibition, while molecules that carried a phenolic group were also evaluated for their ability to inhibit lipid peroxidation. A representative group of compounds were studied in vivo for their anti-inflammatory activity with very encouraging results in paw-induced edema in mice. The 3,4-dimethoxycinnamic and sinapic acid esters with a two-carbon linker exhibited the strongest inhibition of AChE with nanomolar values of IC50. In addition, the sinapic esters demonstrated the highest antioxidant and anti-inflammatory activity. Thus, the above results indicate that the new sinapic acid derivatives based on donepezil combine anti-AChE, anti-inflammatory, and antioxidant activities, which warrant their further evaluation as new lead compounds in the treatment of related neurodegenerative diseases.

PMID 42271174
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PubMedPharmaceutical research2026-06-10

Dead-Space Microdomains as Explicit Barriers to Extracellular Drug Transport in Alzheimer's Disease.

Charemis Dimitrios D, Lampropoulos Dimitrios D, Dimakopoulos Yannis Y, Sivolapenko Gregory G et al.

The impact of dead-space (DS) microdomains on cerebral drug penetration has been demonstrated experimentally; yet computational models typically capture their effects indirectly through effective tortuosity parameters. Here, we develop an anatomically grounded framework that systematically evaluates pharmaceutical diffusion within the central nervous system (CNS). A finite element (FE) model was developed with DS explicitly represented as impermeable obstructions in the extracellular space (ECS) - consistent with structural remodeling observed in Alzheimer's disease (AD). The model was calibrated by reproducing experimental diffusion timescales and subsequently applied to quantify the geometric contribution of DS to pharmaceutical transport. Transport hindrance exhibited a strong dependence on molecular size. Within a representative ECS unit, the arrival of the 0.5 c 0 concentration contour at the venule was delayed by 11 s for Memantine, 14 s for Donepezil, and 80 s for Aducanumab. Spatial analyses revealed penetration delays that were not captured by domain-averaged uptake metrics. A Péclet number analysis confirmed that ECS transport for all three compounds remains diffusion-dominated under neurodegenerative conditions. The proposed framework provides a computationally efficient foundation for predictive multiphysics modeling in the human CNS and demonstrates how local ECS obstructions can lead to therapeutic hindrance in AD.

PMID 42265487
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PubMedJournal of ethnopharmacology2026-06-10

Neuroprotective Effects of Aqueous Extract of Pterocarpus mildbraedii Harms. on Some Biochemical Markers in Alzheimer's Disease Using an AlCl3-induced Rat Model: Integrated ADMET, Network Pharmacology, Molecular Docking, and In Vivo Experimental Validation.

Sandrine Mengue Ngadena Yolande MNY, Blondelle Njoupoue Marie NM, Franklin Zemo Gamo ZG, Emmanuel Owona Pascal OP et al.

Neurodegenerative diseases such as Alzheimer's often lack effective conventional treatments. Phytotherapy is emerging as a promising approach to managing these conditions. Pterocarpus mildbraedii Harms. (P. mildbraedii), a plant from the Fabaceae family, which is traditionally used to treat convulsions, headaches, and fever. This study is designed to evaluate the neuroprotective effects of the aqueous extract of Pterocarpus mildbraedii Harms. on biochemical markers of Alzheimer's disease in an AlCl3-induced rat model using integrated ADMET, network pharmacology, molecular docking, and in vivo validation. We employed network pharmacology and in silico molecular docking to identify bioactive compounds and assess their binding affinities to key proteins: VCP, MAPK1, MMP9, PTGS1, IL6, and AR. The in vivo experiment lasted 56 days, with 30 animals divided into 5 groups (n = 6 per group). They received daily oral doses of distilled water (10 mL/kg), AlCl3 (75 mg/kg), Donepezil (5 mg/kg) after AlCl3, or P. mildbraedii bark water extract at 150 mg/kg (PM 150) and 300 mg/kg (PM 300) following AlCl3. On Days 23 and 51, all animals underwent open-field and Morris water maze tests. On Day 57, animals were sacrificed, and calcium levels, oxidative markers, and neurotransmitter levels were measured in homogenates from the amygdala, hippocampus, and prefrontal cortex. Histopathological analysis of the hippocampus and amygdala was also conducted. In silico studies showed that the plant compounds pterocarpan and liquiritigenin bound strongly to VCP, MAPK1, and MMP9, with binding energies lower than those of reference inhibitors, indicating greater stability. In vivo, AlCl3 caused anxiety, locomotor issues (p< 0. 001), memory impairment (p< 0. 001), and disrupted GABA, ACh metabolism, and AChE activity. It also reduced antioxidant levels (p< 0.001), increased pro-oxidants (p< 0.001), and elevated calcium and Tau protein levels compared to the normal control. Treatment with Pterocarpus mildbraedii extract mitigated these effects, reducing anxiety and enhancing memory, locomotion, ACh, and GABA levels, as well as AChE activity. The extract notably decreased Tau protein and MDA concentrations by 80. 57% in the amygdala, 63. 80.57% in the prefrontal cortex, and 63.73. 50% in the hippocampus, and nitrites. It also significantly increased protein levels, GSH (by 6.95-fold in the amygdala, 80.48% in the prefrontal cortex, and 85.75% in the hippocampus), SOD, and catalase activities across brain regions compared with the AlCl3-treated group. These findings suggest that Pterocarpus mildbraedii extract, with its antioxidant, anti-amnesic, and anxiolytic properties, offers neuroprotection and may have neuroprotective effects in Alzheimer 's-like neurotoxicity.

PMID 42263916
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PubMedMolecular pharmaceutics2026-06-10

Therapeutic Potential of Stearylamine-Conjugated Phenylboronic Acid-Modified Nanocarriers of 4-Allyl Pyrocatechol in Modulating Sialylation and Neuroinflammation in Scopolamine-Induced Cognitive Impairment in the Rat Model.

Katti Vijay Babu VB, Kolusu Aravinda Sai AS, Madhana Rajaram Mohanrao RM, Pindiprolu Sai Kiran S S SKSS et al.

Alzheimer's disease is a progressive neurodegenerative condition and is regarded as the most prevalent type of dementia among older adults. It is characterized by the accumulation of beta-amyloid, tau protein hyperphosphorylation, cholinergic dysfunction, oxidative stress, neuroinflammation, and neuronal loss, all of which contribute to the gradual decline in cognitive function. Recent research has highlighted the role of sialylation in the pathogenesis of Alzheimer's disease. Sialylation plays a critical role in the pathophysiology of Alzheimer's disease, influencing amyloid plaque formation, neuroinflammation, and synaptic function. CD33 plays a significant role in regulating immune responses, particularly in the central nervous system, and has been implicated in the progression of Alzheimer's disease. In this study, we explore the neuroprotective effect of stearylamine-conjugated phenyl boronic acid-modified 4-allyl pyrocatechol (PAPS) nanoparticles in modulating sialylation and neuroinflammation against scopolamine-induced Alzheimer's disease in rats. 4-Allyl pyrocatechol is known to possess antioxidant and anti-inflammatory activities. On the other hand, stearylamine-conjugated phenyl boronic acid (PBSA) not only is a potential vehicle for delivering drugs or therapeutic agents to the brain but also has a propensity to inhibit the interaction of sialic acid-conjugated ligands with CD33 receptors, which facilitates clearance of amyloid beta through microglia-mediated phagocytosis. A total of 36 animals were divided into 6 groups (n = 6) as control group, disease group, standard group, PBSA carrier group, 4-allyl pyrocatechol group, and PAPS group, which were treated with 5% carboxy methyl cellulose (p.o.), scopolamine 3 mg/kg (i.p.), donepezil 3 mg/kg (i.p.), stearylamine-conjugated phenyl boronic acid 2 mL/kg (p.o.), 4-allyl pyrocatechol 10 mg/kg (p.o.), and PAPS 10 mg/kg (p.o.) respectively. The study was designed for 16 days. From day 8, all the groups except the control group were administered scopolamine 3 mg/kg (i.p.) 45 min before they were given their respective treatments. Behavioral tests (open field test, novel object recognition test, Y-maze, and Morris' water maze) were conducted from day 8 to day 15. On day 16, animals were euthanized by cervical dislocation, brains were isolated, and the hippocampus and prefrontal cortex were separated and homogenized, followed by centrifugation at 4 °C, 10,000 rpm for 15 min. The biochemical estimations like acetylcholinesterase activity were used; oxidative and antioxidant parameters like nitric oxide, malondialdehyde, and reduced glutathione were determined; enzyme-linked immunosorbent assays for amyloid beta, inflammatory cytokines, brain-derived neurotrophic factor, and CD33 were performed. The results from behavioral and biochemical tests suggested that the PAPS formulation had a more significant impact on slowing the progression of scopolamine-induced cognitive impairment compared to the stearylamine-conjugated phenyl boronic acid carrier and 4-allyl pyrocatechol alone treatments. The histopathological studies revealed a decline in neural degeneration and showed improved neuronal morphology in the PAPS-treated group compared with the disease group. From the data obtained, the PAPS nanoparticle formulation would be an effective strategy for reducing the progression of cognitive impairment.

PMID 42267754
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PubMedFrontiers in chemistry2026-06-05

Entropy estimation in acetylcholinesterase-donepezil interaction through topological indices: a graph theoretical perspective.

Gayathri K B KB, Roy S S, Jyothish K K

In this work, we investigate the molecular interaction between acetylcholinesterase (AChE) and the Alzheimer's medication donepezil using a graph-theoretical approach. We have presented the molecular graphs of AChE, donepezil, and their docked complex and calculated a set of degree-based topological indices, along with their respective Shannon entropy values. The entropy values measure the structural complexity and information content integral to each molecular graph. The study indicated a uniform growth of entropy for all indices in the docked complex over the unbound protein and ligand, signifying an enhancement in its topological disorder and edge-type variability with binding. It is interesting to see that indices such as the First Zagreb Index, Atom-Bond Connectivity Index, and Randić Index were successful in capturing this trend. This entropy-based assessment offers a solid and computationally efficient method for defining biomolecular interactions and providing insights into binding-induced structural reorganization. The results emphasize the value of topological entropy as a predictive tool for drug-target interaction profiling and structure-based drug design. Thus, the present study offers a computational approach to comprehend and forecast the energetics of a particular protein-ligand binding, which is a crucial objective in drug development and biophysical chemistry.

PMID 42245826
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PubMedMetabolic brain disease2026-06-04

Cannabidiol attenuates tau hyperphosphorylation and cognitive deficits in an experimental model of Alzheimer's disease and is associated with restoration of PP2A expression.

Sura Sreenivasulu S, Jagadeesan Saravanan S, Okwuofu Emmanuel Oshiogwe EO, Dandala Krishna Chaitanya Reddy KCR et al.

Pathogenic tau hyperphosphorylation, together with reduced protein phosphatase 2 A (PP2A) expression, is associated with neurofibrillary tangle formation and cognitive deterioration in Alzheimer's disease (AD). Cannabidiol (CBD), a non-psychotropic phytocannabinoid, remains insufficiently studied for its potential to modulate the PP2A-tau axis in experimental AD. This study evaluated whether CBD improves hippocampus-dependent spatial cognition in a D-galactose/AlCl₃ rat model of AD and whether these effects are associated with restoration of PP2A expression and attenuation of tau hyperphosphorylation. AD-like pathology was induced in male Wistar rats by D-galactose (60 mg/kg i.p.) and AlCl₃ (200 mg/kg oral gavage) for 10 weeks, followed by CBD (20, 40 or 80 mg/kg) or donepezil (1 mg/kg) for three weeks. The Morris water maze, Jess Simple Western, and ELISA were used to assess cognition, PP2A expression, and p-tau levels, respectively. CBD significantly improved spatial learning and memory. PP2A expression increased across all tested doses, with the highest mean level observed at 80 mg/kg. Hippocampal p-tau levels were significantly increased in the model group and significantly reduced by all CBD doses and donepezil (all p < 0.0001 vs. model). The inverse relationship between PP2A expression and p-tau levels suggests possible involvement of the PP2A-tau axis. CBD attenuated cognitive deficits and tau hyperphosphorylation alongside restoration of PP2A expression, suggesting that the PP2A-tau axis may be a relevant therapeutic target in AD-related tauopathy.

PMID 42240860
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