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DO

donepezil (IPI301 / donepezil, iCure / Donerion)

✓ Approved

Icure Pharmaceutical Incorporation · ACHE · Small Molecule

What is donepezil?

donepezil is a small molecule developed by Icure Pharmaceutical Incorporation. It is approved for therapeutic indications via transdermal.

Drug Profile

Brand NamesIPI301, donepezil, iCure, Donerion
CompanyIcure Pharmaceutical Incorporation
Drug ClassSmall Molecule
Molecular TargetACHE
RouteTransdermal
StatusApproved
Sources: ClinicalTrials.gov, Icure Pharmaceutical Incorporation

Mechanism of Action

Molecular Targets

donepezil acts on 1 molecular target:

ACHEacetylcholinesterase (Cartwright blood group) (N-ACHE, ACEE)
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Therapeutic Indications

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

Therapeutic AreaConditionPhase
Nervous system disordersDementia Alzheimer's type✓ Approved

Related Research Articles

PubMedNeuromolecular medicine2026-08-30

AMBMP Hydrochloride Reverses STZ-Induced Alzheimer-Type Dementia Associated with Wnt/β-catenin/TLR4 Signaling.

Kalra Palak P, Chaturvedi Deepak D, Kumar Amit A, Grewal Amarjot Kaur AK et al.

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder with progressive cognitive decline and neuronal loss. This study investigated the neuroprotective effects of AMBMP Hydrochloride, a Wnt/β-catenin agonist, in a streptozotocin (STZ)-induced mice model of AD, elucidating the interplay between dysregulated Wnt/β-catenin signaling and Toll-Like Receptor 4 (TLR4)-mediated inflammation, with Palmitic acid used as a TLR4 pathway modulator. Mice received bilateral intracerebroventricular (i.c.v.) injections of STZ (3 mg/kg) on Day 1 and Day 3, followed by administration of Donepezil (3 mg/kg)/ AMBMP Hydrochloride (5 mg/kg and 10 mg/kg)/Palmitic acid (TLR4 agonist, 20 mg/kg) via the intraperitoneal (i.p.) route from Day 4 to Day 22. STZ-treated mice exhibited significant cognitive dysfunction, characterized by impaired performance in the Morris Water Maze (MWM) task along with increase in acetylcholinesterase (AChE) activity, oxidative stress (thiobarbituric acid reactive substances; TBARS), neuroinflammation [tumor necrosis factor alpha (TNF-α)/Interleukin-6 (IL-6)/Interleukin-1 beta (IL-1β) and nuclear factor kappa B (NF-κB)] and decreased reduced glutathione (GSH) levels. However, AMBMP Hydrochloride significantly improved behavioral and biochemical alterations possibly through modulation of Wnt/β-catenin signaling and attenuation of TLR4-mediated inflammation. Interestingly, Palmitic acid co-treatment was found to counteract these protective effects, further pointing to a role of TLR4 in the pharmacological effect of AMBMP Hydrochloride. In summary, we confirmed that AMBMP Hydrochloride exhibits potent neuroprotective effects associated with modulating Wnt/β-catenin/TLR4 signaling, offering a promising therapeutic approach against Alzheimer-Type Dementia. Future studies should delve deeper into the molecular mechanisms and translational promise of AMBMP hydrochloride, paving the way for its development as a potential candidate for AD management.

PMID 42668333
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PubMedRSC advances2026-08-29

Design and synthesis of quinoline-derived thioureas as potential antihyperglycemic, anti-Alzheimer, and antioxidant agents.

Seraj Faiza F, Maqbool Maryam M, Ali Fayaz F, Chigurupati Sridevi S et al.

A library of quinoline-based thiourea hybrids 1-41 was synthesized via a single-step reaction scheme. All compounds were evaluated for their inhibitory potential against α-amylase, α-glucosidase, AChE, and BChE enzymes as well as for DPPH radical scavenging activity. Among forty-one compounds, 27-31 and 33-37 showed excellent inhibition against α-amylase (IC50 = 18.36-28.21 µM) and α-glucosidase (IC50 = 17.77-29.31 µM) compared to the standard acarbose (IC50 = 16.98 ± 0.12, 14.19 ± 0.06 µM). Moreover, compounds 27, 28, 30, 31, 34, 35, and 37 inhibited AChE (IC50 = 5.60-14.97 µM) and BChE (IC50 = 6.99-15.70 µM) with greater potency than the standard donepezil chloride (IC50 = 1.49 ± 0.13, 2.39 ± 0.06 µM). Kinetic analyses were conducted for the most active compounds to elucidate their modes of enzyme inhibition. Furthermore, molecular docking studies were conducted to explore ligand binding interactions within the enzyme active site. All synthesized derivatives were further evaluated for their DPPH radical scavenging activity, among which compounds 27, 28, 30, 31, 34, and 35 exhibited significant to moderate antioxidant potential (SC50 = 23.92-34.73 µM) compared with the reference standard ascorbic acid (SC50 = 18.28 ± 0.15 µM). Among this library, compound 31, with a difluoro group on the phenyl ring, was identified as the most potent inhibitor against all enzymes. Thus, this study suggests that the reported compounds hold the potential to be further advanced as lead anti-Alzheimer and anti-diabetic agents.

PMID 42666544
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PubMedACS omega2026-08-28

Modulation of Donepezil Release Through Hydrophobic Ion- Pairing with Oleic Acid in Liquid Crystalline Nanodispersions for Transdermal Delivery.

Pires da Silva Priscila P, Marques Victor Cavalcanti VC, Santiago Ramos Lorena Kelly LK, Filho José Dias de Souza JDS et al.

Precursor liquid crystals based on unsaturated monoglycerides, with or without oleic acid (OA), exhibited anisotropy characteristic of an inverse hexagonal phase. Donepezil-loaded liquid crystalline nanodispersions (LCNs) were produced by sonication and exhibited encapsulation efficiencies of 91.3-97.9%, with the OA-containing formulation (LCN-2) displaying a smaller particle size (183.0 ± 1.5 nm), lower polydispersity (0.183 ± 0.006), and improved colloidal stability over 90 days. NMR (1H NMR, 1D NOESY/ROESY and DOSY), molecular docking, and molecular dynamics simulations consistently demonstrated hydrophobic ion-pair formation between donepezil and oleic acid. These molecular interactions reduced drug mobility within the lipid domains, resulting in anomalous release behavior (n = 0.79), more sustained in vitro release, and an approximately 45% higher steady-state skin flux than the control donepezil solution. Overall, hydrophobic ion-pair formation with oleic acid represents an effective strategy to modulate drug release and enhance the transdermal performance of liquid crystalline nanodispersions for donepezil delivery.

PMID 42662756
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PubMedJournal of integrative medicine2026-08-28

Acupuncture for Alzheimer's disease: A systematic review and meta-analysis integrating traditional insights and scientific evidence.

Huang Wei-Ling WL, Wang Li-Li LL, Shi Jian-Rong JR, Liu Qing Q

Alzheimer's disease (AD), a leading cause of dementia in the elderly, is characterized by progressive cognitive impairment, and still lacks effective therapeutic interventions. This systematic review synthesizes the classical theoretical foundations, clinical evidence, and modern mechanistic insights for the use of acupuncture to treat AD. A meta-analysis was conducted based on a comprehensive literature search of PubMed, Embase, the Cochrane Library, CNKI, VIP information, and Wanfang Data, covering the period from inception until September 2025. Eligible randomized controlled trials (RCTs) compared acupuncture (manual or electroacupuncture) with control interventions, including sham acupuncture, donepezil, placebo, or no treatment. Data were extracted by two reviewers working independently and then analyzed using the meta and meta for packages in R (v4.3.2). Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated. A total of 21 RCTs comprising 1354 participants met the inclusion criteria. Compared with no-treatment controls, acupuncture significantly improved cognitive performance, as measured by the Mini-Mental State Examination (MMSE) (WMD = 3.74, 95% CI: 1.34-6.14), and outperformed placebo controls (WMD = 2.13, 95% CI: 1.39-2.87). Acupuncture showed efficacy comparable to that of donepezil on MMSE and Activity of Daily Living (ADL), suggesting non-inferiority to standard pharmacotherapy. Frequently used acupoints included GV20, ST36, GB20, LR3, and ST40, often combining local (GV24, EX-HN1) and distal (SP10, KI3) points. Reported adverse events were mild and transient, with no significant difference from controls. Biomarker analyses indicated that acupuncture enhanced acetylcholine levels and reduced plasma Aβ1-40, Aβ1-42, and Tau levels, implying modulation of cholinergic transmission and AD-related pathology. This review highlights acupuncture as a holistic, multi-targeted therapy with promising potential for managing AD. Future research should aim to standardize acupuncture protocols, integrate TCM syndrome differentiation, and adopt neurobiological and imaging techniques to explore mechanisms. Please cite this article as: Huang WL, Wang LL, Shi JR, Liu Q. Acupuncture for Alzheimer's disease: A systematic review and meta-analysis integrating traditional insights and scientific evidence. J Integr Med. 2026; Epub ahead of print.

PMID 42665452
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PubMedFrontiers in aging neuroscience2026-08-28

The molecular mechanisms of Guizhi Fuling Pills in ameliorating Alzheimer's disease-like cognitive impairment: insights from transcriptomics, metabolomics, and gut microbiome.

Ma Lan L, Wang Jing J, Xu Zhenghao Z, Huang Zuxiu Z et al.

Alzheimer's disease (AD)-like cognitive impairment, as a major type of cognitive disorder, has witnessed a sharp rise in prevalence. Therefore, there is an urgent need to develop effective therapeutic intervention measures. Guizhi Fuling Pills (GFP), a classical Traditional Chinese Medicine (TCM) formula, has been shown to exert protective effects on cognitive function. However, its underlying mechanisms remain unclear. To investigate the effects of GFP on AD-like cognitive impairment and elucidate its underlying mechanisms. D-galactose (D-gal)-induced aged mice were used as the model. Mice were administered via gavage for 4 weeks with 0.9% normal saline (0.1 mL/10 g/d), low-dose GFP (12.56 g/kg/d), medium-dose GFP (25.11 g/kg/d), high-dose GFP (50.22 g/kg/d), and donepezil (5 mg/kg/d). A behavioral test was conducted using the Morris water maze. Histopathological changes were observed via H&E staining and immunohistochemistry (IHC). In addition, various methods such as transcriptomics, metabolomics, network pharmacology, and analysis of gut microbiota were utilized to elucidate the possible mechanisms. Guizhi Fuling Pills improved learning and memory function in aged mice, ameliorated hippocampal neuronal morphology, and reduced p-Tau protein deposition. Network pharmacology and hippocampal transcriptomic analyses suggested that the active components in GFP may ameliorate cognitive impairment through multiple mechanisms. It included regulation of the VEGF and PI3K/AKT signaling pathways, attenuation of inflammatory responses, inhibition of apoptosis, and repair of the blood-brain barrier (BBB). Gut microbiota analysis revealed that GFP modulated the compositional structure of the gut microbiota, including increasing the abundance of Lactobacillales and decreasing Desulfovibrionia and Tannerellaceae. Metabolomics suggested that GFP may ameliorate metabolic disorders in aged mice by modulating the synthesis of lipids and lipid-like molecules. The findings of this study suggest that GFP may ameliorate cognitive dysfunction in AD-like cognitive impairment mice through multiple mechanisms, including repair of the BBB, attenuation of inflammatory responses, and modulation of the gut microbiota and metabolic disorders.

PMID 42661899
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PubMedZhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae2026-08-28

Traditional Chinese Herbal Formula YA3D3 Ameliorates Alzheimer's Disease-Like Pathology and Cognitive Impairment in APP/PS1 Transgenic Mice.

Yang Tian T, Ma Jia-Rui JR, Liang Si-Yao SY, Zhang Yue-Meng YM et al.

Objective To evaluate the effects of the traditional Chinese herbal formula YA3D3 on cognitive impairment and cerebral β-amyloid （Aβ） deposition in APP/PS1 transgenic mice and to determine whether these effects are mediated by up-regulation of the autophagy-related gene 14 （ATG14）. Methods Network pharmacology was employed to predict YA3D3 targets.Total antioxidant capacity and hydroxyl free radical scavenging activity were measured in vitro.BV2 microglial cells were infected with short hairpin RNA （shRNA） lentivirus targeting ATG14 （designated as sh-ATG14） and then treated with 0.5 mg/mL of either water-extract （YA3D3-HF） or fermented （YA3D3-MHF） preparation for 24 h.The expression levels of ATG14 and downstream ATG16L1 were assessed by qPCR and Western blot.Sixty-four 3-month-old male APP/PS1 mice were randomly allocated to eight groups （n=8）：APP/PS1 model，donepezil，low-，medium-，and high-dose YA3D3-HF，and low-，medium-，and high-dose YA3D3-MHF.All the drugs were administered ad libitum in drinking water for 90 days.Spatial learning and memory were evaluated through the Morris water maze.Cerebral Aβ deposition was quantified by immunofluorescence.Autophagy-related gene expression in the brain tissue was analyzed by qPCR. Results Network pharmacology indicated significant enrichment of YA3D3 targets in autophagy and phosphatidylinositol 3-kinase/protein kinase B signaling pathways.YA3D3-MHF showed stronger antioxidant activity than YA3D3-HF in vitro （P<0.001）.In BV2 cells，both preparations reversed ATG14 knock-down-induced down-regulation in the expression of ATG14 and ATG16L1，with YA3D3-MHF being more potent （P=0.003）.The animal experiment showed that all the YA3D3 groups exhibited shorter escape latency and more platform crossings than the APP/PS1 model group （all P<0.05），along with reduced Aβ fluorescence intensity （all P<0.001）.The efficacy of high-dose YA3D3-MHF was similar to that of donepezil.qPCR confirmed that YA3D3 up-regulated the expression of ATG14 and modulated the expression of downstream autophagy-related genes in the brain tissue （all P<0.05）. Conclusions The traditional Chinese herbal formula YA3D3 may up-regulate the expression of ATG14 to slow down Aβ deposition and ameliorate cognitive impairment in APP/PS1 mice，serving as a potential candidate for Alzheimer's disease intervention.It should be noted that this study has not directly verified the necessity of ATG14 in vivo，and the causal relationship between the in vivo therapeutic efficacy of YA3D3 and the up-regulation of ATG14 requires further confirmation.In addition，this study only verifies the expression regulation of autophagy-related molecules and does not confirm the enhancement of autophagy flux.

PMID 42660828
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