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Donepezil(E 2020) is a specific and potent AChE inhibitor for bAChE and hAChE with IC50 of 8.12 nM and 11.6 nM, respectively.
Donepezil has reversible and noncompetitive inhibition effects on AChE. It has 500-1000-fold more selective for AChE over butyrylcholinesterase (BuChE). Short- and long-exposure of SH-SY5Y human neuroblastoma cells to donepezil induces a concentration-dependent inhibition of cell proliferation unrelated to muscarinic or nicotinic receptor blockade or apoptosis. Donepezil reduces the number of cells in the S-G2/M phases of the cell cycle, increases the G0/G1 population, and reduces the expression of two cyclins of the G1/S and G2/M transitions, cyclin E and cyclin B, in parallel with an increase in the expression of the cell cycle inhibitor p21.
Donepezil is metabolized in the liver via the cytochrome P450 system (CYP1A2-, CYP2D6-, CYP3A4-related enzymes). In animals, donepezil is found unchanged in brain, and no metabolites are detected in the nervous tissue. In plasma, urine, and bile, most donepezil metabolites are O-glucuronides. After oral ingestion, peak plasma concentrations are achieved in 3-5 hours and its absortion is not affected by food. Donepezil has linear pharmacokinetics over a dose range of 1-10 mg/day. 96% of circulating donepezil is protein bound.
Immunity. 2025 Jul 8;58(7):1847-1861.e9.
Optogenetic vagal nerve stimulation attenuates heart failure by limiting the generation of monocyte-derived inflammatory CCRL2+ macrophages
Donepezil purchased from AbMole
| Cell Experiment | |
|---|---|
| Cell lines | retinal ganglion cells (RGCs) |
| Preparation method | RGC survival after exposure to each reagent (glutamate, donepezil, tacrine, galanthamine, and HA14-1) is measured by calcein-AM staining after 3 days in culture, Briefly, cells are incubated in 1 μM calcein-AM in PBS for 15 minutes at 37℃. After the medium is replaced with fresh PBS, cells are examined under a fluorescence microscope using a fluorescein filter. The total number of surviving RGCs defined as cells with a calcein-AM stained cell body and a process extending at least two cell diameters from the cell body is counted in each well. The number of surviving RGCs without any drug served as a control. |
| Concentrations | 100 nM-10 μM |
| Incubation time | 3 days |
| Animal Experiment | |
|---|---|
| Animal models | Age-matched (10-12 weeks old, 21–24 g) male C57BL/6 wild-type and CGRP(−/−) mice |
| Formulation | added to the food powder |
| Dosages | 1.5 mg/kg |
| Administration | oral |
| Molecular Weight | 379.49 |
| Formula | C24H29NO3 |
| CAS Number | 120014-06-4 |
| Solubility (25°C) | DMSO: 70 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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