| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Donepezil is a potent, specific, non-competitive and reversible acetylcholinesterase (AChE) inhibitor that elevates synaptic acetylcholine and improves cognitive function in Alzheimer's disease; the 5-O-desmethyl metabolite retains the benzylpiperidine pharmacophore and is expected to interact with AChE, though with lower potency than the parent.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
The deuterated metabolite serves primarily as an internal standard; unlabeled 5-O-desmethyl donepezil is a donepezil metabolite with substantially weaker AChE inhibition than the parent, and its formation is used as a CYP2D6/3A4 activity index in human liver microsome and hepatocyte assays, with the d5 standard enabling precise quantification of metabolite flux. |
| ln Vivo |
In vivo, 5-O-desmethyl donepezil is a circulating donepezil metabolite in humans and preclinical species; the d5 internal standard supports LC-MS/MS quantification of metabolite exposure in plasma and brain, and metabolite/parent ratios are used to assess CYP-mediated metabolic clearance and potential drug interactions affecting donepezil disposition.
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| Enzyme Assay |
AChE inhibition is measured spectrophotometrically using acetylthiocholine as substrate and Ellman's reagent (DTNB) to detect thiocholine production at 412 nm; compound is pre-incubated with recombinant human AChE or brain homogenate before substrate addition, and IC50 is derived from dose-response curves, with the d5 standard spiked into samples for quantification of the unlabeled metabolite in enzyme incubation matrices.
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| Cell Assay |
Human neuroblastoma (SH-SY5Y) or AChE-expressing cells are treated with 5-O-desmethyl donepezil-d5 or unlabeled metabolite, and AChE activity is measured in cell lysates by the Ellman assay; acetylcholine levels in extracellular medium are quantified by LC-MS/MS, and neuroprotection against amyloid-β or glutamate toxicity is assessed by MTT to capture the functional consequence of cholinesterase inhibition.
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| Animal Protocol |
In vivo PK studies administer donepezil or the unlabeled metabolite to rats or dogs, collect plasma and brain at defined time points, and quantify 5-O-desmethyl donepezil by LC-MS/MS using the d5 internal standard; metabolite-to-parent AUC ratios are calculated to estimate metabolic conversion, and brain-to-plasma ratios are determined to assess CNS exposure of the metabolite relative to donepezil.
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| References |
| Molecular Formula |
C23H27NO3
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|---|---|
| Molecular Weight |
365.465
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| Exact Mass |
370.23
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| CAS # |
1189929-21-2
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| Related CAS # |
5-O-Desmethyl donepezil
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| PubChem CID |
45038882
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.996
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| tPSA |
49.77
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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 |
5
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| Heavy Atom Count |
27
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| Complexity |
496
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(O)C=C2CC(CC3CCN(CC4=C([2H])C([2H])=C([2H])C([2H])=C4[2H])CC3)C(=O)C2=C1
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| InChi Key |
DSMISVLYMKJMLP-VIQYUKPQSA-N
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| InChi Code |
InChI=1S/C23H27NO3/c1-27-22-14-20-18(13-21(22)25)12-19(23(20)26)11-16-7-9-24(10-8-16)15-17-5-3-2-4-6-17/h2-6,13-14,16,19,25H,7-12,15H2,1H3/i2D,3D,4D,5D,6D
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| Chemical Name |
5-hydroxy-6-methoxy-2-[[1-[(2,3,4,5,6-pentadeuteriophenyl)methyl]piperidin-4-yl]methyl]-2,3-dihydroinden-1-one
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7362 mL | 13.6810 mL | 27.3620 mL | |
| 5 mM | 0.5472 mL | 2.7362 mL | 5.4724 mL | |
| 10 mM | 0.2736 mL | 1.3681 mL | 2.7362 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.
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