An AChE inhibitor
Donepezil is an inhibitor of acetylcholinesterase (AChE; IC50 = 6.7 nM).1 It is selective for AChE over butyrylcholinesterase (BChE; IC50 = 988 nM). Donepezil (0.1 and 1 ?M) inhibits the production of nitric oxide (NO) and TNF-α induced by oligomeric amyloid-β (1-42) (AβO1-42) in primary rat microglial cells.2 It increases ACh levels in the cortex and hippocampus of aged rats when administered at a dose of 1.5 mg/kg.3 Donepezil (2 mg/kg) reduces Mac-1 and GFAP protein expression, markers of microglia and astrocyte activation, respectively, in the hippocampal dentate gyrus of a mouse model of Alzheimer’s disease induced by intrahippocampal injection of AβO1-42.2 It increases step-through latency in a passive avoidance test in the same model. Formulations containing donepezil have been used in the treatment of Alzheimer’s disease.
1.Cacabelos, R.Donepezil in Alzheimer's disease: From conventional trials to pharmacogeneticsNeuropsychiatr. Dis. Treat.3(3)303-333(2007) 2.Kim, H.G., Moon, M., Choi, J.G., et al.Donepezil inhibits the amyloid-beta oligomer-induced microglial activation in vitro and in vivoNeurotoxicology4023-32(2014) 3.Scali, C., Casamenti, F., Bellucci, A., et al.Effect of subchronic administration of metrifonate, rivastigmine and donepezil on brain acetylcholine in aged F344 ratsJ. Neural Transm. (Vienna)109(7-8)1067-1080(2002)
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