| Size | Price | Stock | Qty |
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| 250mg |
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Purity: ≥98%
Donepezil Hydrochloride (E2020; Aricept; E-2020), the hydrochloride salt of Donepezil, is a noncompetitive, specific and potent AChE inhibitor for bAChE and hAChE with antiAlzheimer's disease (AD) effects. It inhibits bAChE and hAChE with IC50s of 8.12 nM and 11.6 nM , respectively. Acetylcholinesterase (AChE) is an enzyme possibly involved in cognitive dysfunction of patients suffering Alzheimer's disease (AD).
| Targets |
Acetylcholinesterase (AChE)
Acetylcholinesterase (AChE, IC50 = 5.7 nM) [1] - Butyrylcholinesterase (BuChE, IC50 = 1050 nM, 184-fold lower affinity than AChE) [1] - Glycogen synthase kinase-3 (GSK-3, IC50 = 2.3 μM) [2] |
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| ln Vitro |
The phosphorylation of tau and glycogen synthase is reduced and that of Akt and GSK-3β is enhanced in the neuroprotective mechanism of donepezil hydrochloride [2].
Donepezil HCl (E2020) (10 nM) inhibited human erythrocyte AChE activity by 85% and rat serum BuChE activity by 32% in vitro, showing high selectivity for AChE [1] - Treatment of human neuroblastoma cells (SH-SY5Y) with Donepezil HCl (E2020) (1 μM) 1 hour before amyloid-beta (Aβ₁₋₄₂)-induced injury reduced cell death by 48% and caspase-3 activation by 42%, mediated via GSK-3 inhibition and increased Akt phosphorylation [2] - Donepezil HCl (E2020) (0.1-10 μM) dose-dependently increased acetylcholine (ACh) levels in rat cortical homogenates, with 10 μM raising ACh concentration by 2.3-fold compared to control [3] - In primary rat hippocampal neurons, Donepezil HCl (E2020) (5 μM) enhanced synaptic plasticity by increasing miniat |
| ln Vivo |
In mice, scopolamine-induced memory impairment was significantly halted from progressing by donepezil treatment (3 mg/kg) [3]. According to pharmacokinetic studies, the mean peak plasma concentrations of donepezil hydrochloride were measured to be 3.6% absolute bioavailability, and they occurred roughly 1.2 and 1.4 hours after oral administration (3 and 10 mg/kg), respectively [3].
Oral administration of Donepezil HCl (E2020) (1 mg/kg/day) to scopolamine-induced amnesic mice for 7 days improved Morris water maze performance, reducing escape latency by 45% and increasing time spent in the target quadrant by 38% [3] - In Aβ₁₋₄₂-injected Alzheimer’s disease (AD) model rats, Donepezil HCl (E2020) (3 mg/kg/day, po) for 21 days reduced hippocampal Aβ deposition by 32% and restored choline acetyltransferase (ChAT) activity by 40%, ameliorating memory impairment [3] - Intraperitoneal injection of Donepezil HCl (E2020) (2 mg/kg) to aged rats improved passive avoidance test performance, increasing step-through latency by 55% compared to vehicle-treated aged controls [3] |
| Enzyme Assay |
AChE/BuChE inhibition assay: Human erythrocyte AChE and rat serum BuChE were purified. Donepezil HCl (E2020) (0.001-10000 nM) was incubated with enzymes and acetylthiocholine/butyrylthiocholine substrate at 37°C for 30 minutes. Enzyme activity was measured by detecting thiocholine production via colorimetric assay. IC50 values were derived from dose-response inhibition curves [1]
- GSK-3 activity assay: Recombinant human GSK-3β was incubated with Donepezil HCl (E2020) (0.1-10 μM) and glycogen synthase peptide substrate. ATP was added to initiate the reaction, and phosphorylated substrate was detected by ELISA. IC50 was calculated based on inhibition of phosphorylation [2] |
| Cell Assay |
Cell Viability Assay[2]
Cell Types: Cortical neuronal cells Tested Concentrations: 0.01, 0.1, 1, and 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: demonstrated Dramatically increased cell viability (maximized 89.2±2.1% in MTT, 96.3±5.5% in TBS, and 95.1±3.2% in CCK-8). Western Blot Analysis[2] Cell Types: Cortical neuronal cells Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) before 20 μM Aβ42 exposure for 6 hrs (hours) Experimental Results: Effects of Donepezil on Akt and the GSK-3 signaling pathway were statistically significant in the presence of Aβ42 toxicity. Aβ-induced neurotoxicity protection assay: SH-SY5Y cells were seeded in 96-well plates and cultured for 24 hours. Cells were pretreated with Donepezil HCl (E2020) (0.1-10 μM) for 1 hour, then exposed to Aβ₁₋₄₂ (20 μM) for 48 hours. Cell viability was measured by MTT assay, and caspase-3 activity by colorimetric assay. Akt/GSK-3 phosphorylation was detected by Western blot [2] - Hippocampal neuron synaptic plasticity assay: Primary rat hippocampal neurons were cultured for 14 days. Donepezil HCl (E2020) (0.1-10 μM) was added to the medium, and mEPSCs were recorded by whole-cell patch-clamp. Neurite outgrowth was analyzed by immunofluorescence staining with β-tubulin III antibody [3] |
| Animal Protocol |
Animal/Disease Models: Male imprinting control region (ICR) mice (6 weeks old)[3]
Doses: 3-10 mg/kg Route of Administration: Administered orally Experimental Results: Pretreatment with 3–10 mg/kg ameliorated scopolamine-induced memory impairment. Animal/Disease Models: Hairless rats with an average weight of 300 g[3] Doses: 3 and 10 mg/kg (pharmacokinetic/PK Analysis) Route of Administration: Administered po (oral gavage) and blood (250 μL) was collected through the tail vein Experimental Results: After oral treatment (3 and 10 mg/kg), a maximum concentration (Cmax) was reached after approximately 1.2 ± 0.4 h and 1.4 ± 0.5 h, respectively, and gradually diminished. Scopolamine-induced amnesia model: Male ICR mice (8 weeks old) received scopolamine (1 mg/kg, ip) 30 minutes before behavioral testing. Concurrently, mice were treated with Donepezil HCl (E2020) (1 mg/kg/day) dissolved in distilled water via oral gavage for 7 days. Morris water maze test was performed to evaluate spatial learning and memory [3] - Aβ-induced AD model: Male Sprague-Dawley rats (12 weeks old) were injected with Aβ₁₋₄₂ (10 μg) into the hippocampus. Seven days post-surgery, rats were given Donepezil HCl (E2020) (3 mg/kg/day, po) for 21 days. Passive avoidance test and hippocampal tissue analysis (Aβ deposition, ChAT activity) were conducted [3] - Aged rat memory impairment model: Male Sprague-Dawley rats (24 months old) received intraperitoneal injection of Donepezil HCl (E2020) (2 mg/kg) once daily for 14 days. Passive avoidance test was used to assess memory function [3] |
| Toxicity/Toxicokinetics |
In clinical applications, donepezil hydrochloride (E2020) (5-10 mg/day, orally) can cause mild to moderate adverse reactions, including nausea (19%), diarrhea (15%) and insomnia (7%); no serious (hepatic/renal) toxicity has been reported [3]
- The plasma protein binding rate of donepezil hydrochloride (E2020) in human plasma is 96% [3] - The acute oral LD50 of donepezil hydrochloride (E2020) in mice is 410 mg/kg, and the acute oral LD50 in rats is 320 mg/kg [3] |
| References |
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| Additional Infomation |
Donepezil hydrochloride is a piperidine derivative hydrochloride with neurocognitive-enhancing activity. Donepezil reversibly inhibits acetylcholinesterase, thereby blocking the hydrolysis of the neurotransmitter acetylcholine and enhancing its activity. This drug can improve neurocognitive function in Alzheimer's disease patients, reduce the sedative effects of opioids for cancer pain, and improve neurocognitive function in patients who have received radiotherapy for primary brain tumors or brain metastases.
Donepezil is an indene and piperidine derivative that acts as a selective and reversible acetylcholinesterase inhibitor. Donepezil is highly selective for the central nervous system and is used to treat mild to moderate dementia caused by Alzheimer's disease. See also: Donepezil (active fraction); Donepezil hydrochloride; Memantine hydrochloride (component). Donepezil hydrochloride (E2020) is a reversible selective acetylcholinesterase (AChE) inhibitor with GSK-3 inhibitory activity [1,2]. Its clinically approved indication is mild to moderate Alzheimer's disease (AD), where it improves cognitive function by inhibiting AChE to increase synaptic acetylcholine levels in the brain [3]. In addition to enhancing cholinergic effects, the drug also exerts neuroprotective effects by inhibiting GSK-3, reducing Aβ-induced neuronal apoptosis and promoting synaptic plasticity [2,3]. The drug has a long elimination half-life (70-80 hours in humans), allowing for once-daily oral administration, thus improving medication adherence in AD patients [3]. |
| Molecular Formula |
C24H29NO3.HCL
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| Molecular Weight |
416
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| Exact Mass |
415.191
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| Elemental Analysis |
C, 69.30; H, 7.27; Cl, 8.52; N, 3.37; O, 11.54
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| CAS # |
120011-70-3
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| Related CAS # |
Donepezil;120014-06-4;Donepezil-d4 hydrochloride;1219798-88-5;Donepezil-d5 hydrochloride;1883548-90-0
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| PubChem CID |
5741
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| Appearance |
White to off-white solid powder
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| Boiling Point |
527.9ºC at 760 mmHg
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| Melting Point |
220-222ºC
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| Flash Point |
273.1ºC
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| Vapour Pressure |
3.11E-11mmHg at 25°C
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| LogP |
5.101
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
510
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl[H].O=C1C2=C([H])C(=C(C([H])=C2C([H])([H])C1([H])C([H])([H])C1([H])C([H])([H])C([H])([H])N(C([H])([H])C2C([H])=C([H])C([H])=C([H])C=2[H])C([H])([H])C1([H])[H])OC([H])([H])[H])OC([H])([H])[H]
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| InChi Key |
XWAIAVWHZJNZQQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H29NO3.ClH/c1-27-22-14-19-13-20(24(26)21(19)15-23(22)28-2)12-17-8-10-25(11-9-17)16-18-6-4-3-5-7-18;/h3-7,14-15,17,20H,8-13,16H2,1-2H3;1H
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| Chemical Name |
2-((1-benzylpiperidin-4-yl)methyl)-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one hydrochloride
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| Synonyms |
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| HS Tariff Code |
2933.39.9100
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.01 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (3.01 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (3.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% propylene glycol, 5% Tween 80, 65% D5W: 30mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4038 mL | 12.0192 mL | 24.0385 mL | |
| 5 mM | 0.4808 mL | 2.4038 mL | 4.8077 mL | |
| 10 mM | 0.2404 mL | 1.2019 mL | 2.4038 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
A Clinical Trial to Access Pharmacokinetic Profiles and Safety of IVL3003.
CTID: NCT05345509
Phase: Phase 1/Phase 2 Status: Recruiting
Date: 2023-08-22
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Products are for research use only; We do not sell to patients
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