Donepezil (E2020)

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.Target: AChEDonepezil is a specific and potent AChE inhibitor for bAChE and hAChE with IC50 of 8.12 nM and 11.6 nM , respectively [1]. Donepezil inhibits the carbachol-stimulated increase in intracellular Ca2+ concentration in human SHSY5Y neuroblastoma cells in a concentration dependent manner, indicating that Donepezil have muscarinic antagonist activity. Intraperitoneal administration of Donepezil in rats produces a dose dependent increase in salivation and tremor, which are overt cholinergic behavioural signs, with an ED50 of 6 μmol/kg. Donepezil is found to be somewhat less potent with a ED50 of 50 μmol/kg following oral administration [2]. A recent study shows that Donepezil can protect human umbilical vein endothelial cells (HUVECs) against H2O2-induced cell injury. This may be useful as a potential therapy for oxidative stress in cardiovascular and cerebrovascular diseases [3].

[1]. Ogura, H., et al., Comparison of inhibitory activities of donepezil and other cholinesterase inhibitors on acetylcholinesterase and butyrylcholinesterase in vitro. Methods Find Exp Clin Pharmacol, 2000. 22(8): p. 609-13. [2]. Snape, M.F., et al., A comparative study in rats of the in vitro and in vivo pharmacology of the acetylcholinesterase inhibitors tacrine, donepezil and NXX-066. Neuropharmacology, 1999. 38(1): p. 181-93. [3]. Huang, Z.H., et al., Donepezil protects endothelial cells against hydrogen peroxide-induced cell injury. CNS Neurosci Ther, 2012. 18(2): p. 185-7.