Donepezil (Aricept) is a piperidine-based, potent, specific, and reversible inhibitor of acetylcholinesterase (AChE). It can be used for the treatment of mild to moderate dementia of the Alzheimer's type.

AChE (human):11.6 nM, AChE (bovine):8.12 nM

Donepezil对AChE的选择性比对BuChE（butyrylcholinesterase）高出500-1000倍。无论是短期还是长期暴露，Donepezil均会引起SH-SY5Y人类神经母细胞增殖的浓度依赖性抑制，这种抑制与毒蕈碱或烟碱受体阻断或细胞凋亡无关。Donepezil减少了细胞周期中S-G2/M阶段的细胞数量，增加了G0/G1期的细胞比例，并且与p21细胞周期抑制因子表达量的增加平行，降低了G1/S与G2/M转换期中两种cyclins（cyclin E与cyclin B）的表达。此外，Donepezil增加了依赖动作电位的多巴胺释放，并调节了黑质多巴胺能神经元的烟碱受体[1]。

在血浆、尿液和胆汁中，多数Donepezil的代谢产物为O-葡萄糖醛酸酯。经口摄入后，3-5小时达到血浆峰值浓度，食物不影响其吸收。Donepezil从胃肠道缓慢吸收，年轻志愿者的终末消除半衰期为50-70小时（老年受试者>100小时）。在肝脏经过广泛代谢后，原化合物有93%与血浆蛋白结合。Donepezil在肝脏通过细胞色素P450系统（CYP1A2-、CYP2D6-、CYP3A4相关酶）代谢。在动物中，Donepezil在大脑中未改变，神经组织中未检测到代谢物。Donepezil在1-10 mg/天的剂量范围内具有线性药动学特性。循环中的Donepezil有96%与蛋白质结合[1]。

Cell lines: retinal ganglion cells (RGCs). Concentrations: 0.1-10 μM. Incubation Time: 3 days. RGC survival after exposure to each reagent (glutamate, donepezil, tacrine, galanthamine, and HA14-1) is measured by calcein-AM staining after 3 days in culture, Briefly, cells are incubated in 1 μM calcein-AM in PBS for 15 minutes at 37℃. After the medium is replaced with fresh PBS, cells are examined under a fluorescence microscope using a fluorescein filter. The total number of surviving RGCs defined as cells with a calcein-AM stained cell body and a process extending at least two cell diameters from the cell body is counted in each well. The number of surviving RGCs without any drug served as a control.

Animal Models: male C57BL/6 wild-type and CGRP(?/?) mice (10-12 weeks old, 21–24 g). Formulation: added to the food powder. Dosages: 1.5 mg/kg (i.g.)