Background
Donepezil Hydrochloride (Donepezil HCL) is a novel, potent and selective inhibitor of acetylcholinesterase (AChE), an enzyme possibly involved in cognitive dysfunction of patients suffering Alzheimer’s disease (AD), with the half maximal inhibition concentration IC50 value of 6.7 nM [1].
Donepezil HCL is a piperidine-class AChE inhibitor containing an N-benzylpiperdine and an indanone moiety, which confers it a longer and more selective action against AchE as compared to BuChE (IC50: 7.4 μM) [1].
Donepezil HCL has been approved by FDA for the treatment of AD, in which it has improved cognitive function of mild to severe moderate AD patients and exhibited excellent tolerability without hepatotoxicity [1].
Reference
参考文献:
[1] Sugimoto H, Ogura H, Arai Y, Limura Y, Yamanishi Y. Research and development of donepezil hydrochloride, a new type of acetylcholinesterase inhibitor. Jpn J Pharmacol. 2002 May;89(1):7-20.
Protocol
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Cell experiment [1,2]:
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Cell lines
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Human SHSY5Y neuroblastoma cells, human umbilical vein endothelial cells
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Preparation method
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Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
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Reacting condition
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1 h
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Applications
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Donepezil dose-dependently inhibited the carbachol-stimulated increase in intracellular Ca2+ concentration in human SHSY5Y neuroblastoma cells with the IC50 of 4.0 ± 0.2 μM. Donepezil protected human umbilical vein endothelial cells (HUVECs) against H2O2-induced cell injury. Donepezil (100 μM) decreased cell viability. Pretreatment with donepezil at concentrations of 1 and 10 μM significantly inhibited the H2O2–induced reduction in cell viability. Exposure of HUVECs to donepezil (1 μM) for 2 h upregulated HIF-1α expression.
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Animal experiment [1,3]:
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Animal models
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Male Lister Hooded rats, adult male NMRI mice
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Dosage form
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Intraperitoneal administration, 1 mg/kg
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Application
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In Male Lister Hooded rats, donepezil dose-dependently increased salivation and tremor with an ED50 of 6 μmol/kg. In adult male NMRI mice, donepezil (1 mg/kg) improved recognition performances.
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Other notes
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Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
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参考文献:
[1]. Snape M F, Misra A, Murray T K, et al. A comparative study in rats of the in vitro and in vivo pharmacology of the acetylcholinesterase inhibitors tacrine, donepezil and NXX-066[J]. Neuropharmacology, 1999, 38(1): 181-193.
[2]. Huang Z H, Guo W, Zhang L L, et al. Donepezil protects endothelial cells against hydrogen peroxide‐induced cell injury[J]. CNS neuroscience & therapeutics, 2012, 18(2): 185-187.
[3].Freret T, Bouet V, Quiedeville A, et al. Synergistic effect of acetylcholinesterase inhibition (donepezil) and 5-HT 4 receptor activation (RS67333) on object recognition in mice[J]. Behavioural brain research, 2012, 230(1): 304-308.
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