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Mechanism of Donepezil Protecting Neurons by Inhibiting Sodium Channel and NMDA Receptor Channel

??OBJECTIVE To study the protective effect of donepezil on L-glutamic acid-induced injury and the effects on Na⁺ currents and NMDA receptor-mediated currents in neurons. METHODS Cortical and hippocampal neurons were isolated from postnatal 12 h Wistar rats and were cultured for 8-12 d. The protective effect of donepezil on L-glutamic acid-induced injury in neurons was investigated by MTT cell viability assay, and selective Na⁺ channel blocker TTX and selective NMDA receptor blocker MK-801 were taken as positive drugs. The effects of donepezil on Na⁺ and NMDA receptor-mediated current in hippocampal and cortical neurons was studied by using manual patch clamp. RESULTS Donepezil and MK-801 showed protective effects on L-glutamic acid-induced injury model, and TTX can slightly enhance the protective effect of MK-801. 1 ??mol??L^-1 donepezil slightly inhibited Na⁺ currents and NMDA receptor-mediated currents of hippocampal and cortical neurons and 10 ??mol??L^-1 donepezil showed obviously inhibiting effects on Na⁺ currents and NMDA receptor-mediated currents of hippocampal and cortical neurons. CONCLUSION Donepezil can protect neurons from glutamic acid damage, and its mechanism is related to inhibiting current of Na⁺ channel and NMDA receptor channel.