Donepezil hydrochloride

Potent acetylcholinesterase inhibitor (IC₅₀ = 5.7 nM) which increases acetylcholine levels. Displays >1200-fold selectivity for AChE over butyrylcholinesterase (BuChE). Orally active. Shows anti-inflammatory properties, neuroprotective activity and attenuates amyloid-β load in vitro and in vivo. In combination, donepezil and LSL60101 decrease amyloid-β₄₀ and amyloid-β₄₂ levels, amyloid-β plaque number and tau hyperphosphorylation to attenuate amyloid-β pathology in 5XFAD brains. Chronic low-dose treatment with LSL60101 and donepezil reversed cognitive deficits and impaired social behaviour.