Donepezil

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 µM) inhibits the production of nitric oxide (NO) and TNF-α induced by oligomeric amyloid-β (1-42) (AβO_1-42) 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 AβO_1-42.² 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.

WARNING This product is not for human or veterinary use.

1. Cacabelos, R. Donepezil in Alzheimer’s disease: From conventional trials to pharmacogenetics. Neuropsychiatr. 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 vivo. Neurotoxicology 40, 23-32 (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 rats. J. Neural Transm. (Vienna) 109(7-8), 1067-1080 (2002).