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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

PubMedInternational journal of biological macromolecules2026-07-27

Donepezil nanocrystals-incorporated carboxymethyl cellulose nanopaste for high-payload transdermal delivery with improved skin compatibility.

Yang In Gyu IG, Heo Jae Yoon JY, Myung Jin Hyuk JH, Jeong Min Young MY et al.

Donepezil (DPZ), an acetylcholinesterase inhibitor for Alzheimer's disease, suffers from skin irritation during transdermal delivery. Herein, a drug high-payload nanopaste (NP) system was designed employing carboxymethyl cellulose (CMC) to enhance transdermal delivery of DPZ while mitigating cutaneous irritation. DPZ NPs (10, 20, and 27.5% w/v) were fabricated via wet bead-milling with low-molecular-weight CMC (90 K) to obtain submicron particles, followed by incorporation into high-molecular-weight CMC (700 K) matrix. The drug nanocrystals were uniformly distributed in the CMC matrix, preserving crystal size (505.6-563.8 nm), zeta potential (-48.93 to -51.95 mV), and crystallinity. Fourier-transform infrared analysis revealed the electrostatic interaction between the anionic polymers and drug nanocrystals. Pharmacokinetic evaluations in rats revealed that while the 10% NP achieved systemic absorption comparable to the commercial patch, the 20% NP provided a 2.1-fold higher transdermal absorption. Level A IVIVC analysis established a robust correlation (R2 > 0.96) between in vitro dissolution profile and in vivo absorption. Crucially, the CMC-based NPs showed markedly improved dermal tolerability, showing minimal hyperplasia and inflammation compared to acrylic-based commercial patches. Additionally, NPs were chemically stable under accelerated conditions without antioxidants. These findings suggest that CMC-based NP system of DPZ represents a biocompatible transdermal platform for long-term Alzheimer's therapy.

PMID 42503382
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PubMedPharmacy (Basel, Switzerland)2026-07-27

Cumulative Anticholinergic Burden and Risk of Delirium Among Older Adults with Alzheimer's Disease.

Talwar Ashna A, Sherer Jeffrey J, Abughosh Susan S, Chatterjee Satabdi S et al.

Delirium is a transient neuropsychiatric condition that is a severe and prevalent condition affecting 2.6 million older adults each year. Alzheimer's disease (AD) and anticholinergic medication use are risk factors for delirium. This study evaluated the association between cumulative anticholinergic burden (CAB) and risk of delirium among older adults with AD initiating cholinesterase inhibitors (ChEIs). This retrospective cohort study used 2013-2017 Medicare claims data, and included adults 65 years and older with AD who initiated any of the ChEIs (donepezil, rivastigmine, and galantamine) after a 12-month washout period. CAB, as the primary exposure, was measured on the index date and calculated as the monthly total standardized daily dose of anticholinergic medications. A multivariable Cox proportional hazards regression model with inverse probability of treatment weighting (IPTW) generated using generalized boosted models was used to evaluate the risk of delirium associated with the CAB. This study identified 143,320 older adults with AD who initiated ChEIs. Most patients were in the low/no burden (62.73%) group, followed by high burden (21.12%) and moderate burden (16.14%). Overall, delirium diagnosis was observed in 19.11% of the cohort. The Cox regression model with IPTW found that moderate (aHR, 1.56; 95% CI, 1.52-1.61; p < 0.0001) and high CAB (aHR, 1.45; 95% CI, 1.42-1.49; p < 0.0001) were associated with an increased risk of delirium compared to low/no burden. Among older adults with AD initiating ChEIs, moderate and high CAB were associated with an increased risk of delirium compared with low/no CAB. These findings highlight the need to carefully reduce the CAB, especially dose and duration, along with utilizing anticholinergic alternatives in older adults with AD.

PMID 42506779
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PubMedDose-response : a publication of International Hormesis Society2026-07-26

Cnicin Attenuates Aluminium Chloride-Induced Neurodegeneration Through Antioxidant and Anti-Inflammatory Mechanisms.

Yu Li L, Alhoqail Wardah A WA, Mickymaray Suresh S, Li Fang F

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited disease-modifying therapies. Aluminium chloride (AlCl3)-induced neurotoxicity mimics key pathological features of AD, including oxidative stress, neuroinflammation, and cholinergic dysfunction. This study aimed to evaluate the neuroprotective effect of cnicin in an AlCl3-induced rat model of Alzheimer-like neurodegeneration. Rats were divided into five groups: normal control, AlCl3 control (75 mg/kg/day, p.o.), AlCl3 with cnicin (20 and 40 mg/kg/day, p.o.), and AlCl3 with donepezil (5 mg/kg/day, p.o.) for 30 days. Behavioral performance was assessed using hanging wire and beam walking tests. Biochemical parameters, including acetylcholinesterase (AChE), antioxidant enzymes (SOD, CAT, GSH), malondialdehyde (MDA), and inflammatory cytokines (TNF-α, IL-1β) were analyzed, along with histopathology. AlCl3 administration induced significant behavioral deficits, increased AChE activity, oxidative stress, neuroinflammation, and neuronal damage. Cnicin treatment dose-dependently improved motor function, reduced AChE activity, restored antioxidant levels, decreased lipid peroxidation, and suppressed inflammatory markers. Histological analysis confirmed preservation of neuronal architecture, comparable to that of donepezil. Cnicin exhibits significant neuroprotective effects against AlCl3-induced neurodegeneration by modulating cholinergic activity, oxidative stress, and inflammation, suggesting its potential as a therapeutic agent for AD.

PMID 42502675
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PubMedCureus2026-07-26

Butterfly Glioma of the Corpus Callosum Mimicking Rapidly Progressive Dementia.

Maity Soumyadeep S, Ray Girin G, Gupta Chandra Paul CP, Basu Satyaki S et al.

A butterfly-pattern, high-grade glioma involving the corpus callosum is an uncommon but highly aggressive brain tumour that may present with neuropsychiatric manifestations and mimic rapidly progressive dementia, leading to diagnostic delay. Disruption of frontal-callosal connectivity may produce behavioural and cognitive abnormalities resembling behavioural and psychological symptoms of dementia (BPSD), resulting in initial misdiagnosis. A 65-year-old postmenopausal woman presented with a two-week history of vomiting, progressive disorientation, generalized weakness, irrelevant speech, cognitive decline, and bladder and bowel dysfunction. She had previously been treated for acute-onset dementia with BPSD using donepezil and memantine without prior neuroimaging. Neurological examination revealed asymmetric pyramidal signs, rigidity, and bilaterally constricted pupils. Arterial blood gas analysis showed respiratory alkalosis with hypocalcaemia, and urine culture isolated extended-spectrum beta-lactamase (ESBL)/AmpC-producing Klebsiella aerogenes. Contrast-enhanced MRI demonstrated a greater than 65 × 61 mm solid-cystic heterogeneously enhancing mass involving the genu of the corpus callosum with bifrontal extension and perilesional oedema, favouring a radiologically suspected high-grade glioma involving the corpus callosum. A stereotactic biopsy was planned for histopathological confirmation. The patient received corticosteroids, anti-epileptics, antibiotics, and supportive treatment, with subsequent clinical improvement. This case underscores the importance of early neuroimaging in atypical dementia presentations, especially when focal neurological deficits or signs of raised intracranial pressure are present. Histopathological confirmation remains essential for definitive diagnosis and treatment planning.

PMID 42502551
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PubMedScientific reports2026-07-26

Vitamin a modulates neurogenesis-associated pathways and cholinergic signaling in Alzheimer's disease: potential role of reactive astrocytes via NGN2/SOX-11 and SIRT-1.

El-Mezayen Nesrine Saeid NS, Eesa Yara Alaa YA, Hassan Wed Alaa WA, Aly Dina Ahmed DA et al.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder lacking effective disease-modifying therapies. A promising regenerative approach involves enhancing endogenous neurogenic capacity within the injured brain. Reactive astrocytes-stellate-like cells in the AD brain-may contribute to a pro-neurogenic environment through transcription factors (TFs) such as neurogenin 2 (NGN2) and SOX-11. This process is tightly regulated by epigenetic mechanisms, particularly SIRT-1, a neuroprotective histone deacetylase that modulates TF activity and neuronal fate. Vitamin A (VA), a key regulator of differentiation and epigenetic remodeling via its active metabolite retinoic acid, is stored in astrocytes and hepatic stellate cells (HSCs). We hypothesized that AD-related astrocyte activation depletes cerebral VA, mobilizes hepatic stores, contributes to liver fibrosis, and that VA supplementation may restore astrocytic function, activate endogenous TFs via SIRT-1, and drive cholinergic neuron regeneration. In a scopolamine (SCO)-induced AD rat model, VA biodistribution was traced using confocal microscopy. Brain and liver VA deficiency were confirmed via retinol-binding protein (RBP) and ALDH1A1 expressions. Rats received VA (1500, 3000, or 4500 IU/kg/day) or donepezil. Outcomes included neurogenesis (DCX), NGN2/SOX-11 expression, SIRT-1 activation, cholinergic regeneration, amyloid-β deposition, and serum tau. Liver fibrosis was assessed via TGF-β, hydroxyproline and histopathologically. AD induced systemic VA depletion and liver fibrosis. Medium-dose VA (VAMD) significantly enhanced neurogenesis, TF expression, SIRT-1 activation, cholinergic regeneration, and reversed liver fibrosis. VAMD demonstrated neuroregenerative and antifibrotic effects, indicating a possible therapeutic role in AD.

PMID 42502106
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PubMediScience2026-07-24

Tuberostemonine ameliorates Alzheimer's disease pathology by suppression of the p38 MAPK signaling pathway.

Li Yingzhou Y, Xu Xiaoxia X, Meng Ziyao Z, Chen Linjie L et al.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with limited therapeutic options. Here, we report that tuberostemonine (Tub), an alkaloid from Stemona tuberosa, exerts neuroprotective effects in AD models. In Aβ1-42-treated PC12 cells, Tub reduced cytotoxicity, apoptosis, and oxidative stress while restoring mitochondrial function. In APP/PS1 transgenic mice, Tub administration improved cognitive performance, reduced amyloid-β plaque deposition, attenuated microglial activation, and attenuated neuronal loss, with efficacy superior to donepezil. Mechanistically, Tub selectively inhibited p38 MAPK phosphorylation without affecting ERK or JNK pathways, as confirmed by pharmacological inhibition and activation experiments. These findings identify Tub as a promising multi-target natural compound for AD intervention through p38 MAPK pathway modulation.

PMID 42495541
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