Abstract
The neuroprotective effect of donepezil, an acetylcholinesterase inhibitor on retinal ganglion cells (RGCs), was examined. The survival of purified RGCs after exposure to glutamate with or without donepezil (10(- 7) M to 10(- 5) M) was measured after 3 days in culture. In vivo, the neuroprotective effect of donepezil was examined by quantifying the number of viable RGCs 7 days after axotomy in adult rats. In vitro, donepezil dose-dependently reduced RGC death caused by glutamate toxicity. Oral administration of donepezil (10 mg kg(-1) day(-1)) significantly reduced RGC death after axotomy. In conclusion, donepezil exerts a protective effect on RGCs both in vitro and in vivo.
MeSH terms
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Administration, Oral
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Animals
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Axotomy
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Benzopyrans / pharmacology
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Cell Survival
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Cells, Cultured
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Cholinergic Antagonists / pharmacology
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Cholinesterase Inhibitors / pharmacology*
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Cytoprotection
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Donepezil
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Female
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Glutamic Acid / toxicity
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Indans / pharmacology*
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Mecamylamine / pharmacology
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Neuroprotective Agents / pharmacology*
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Nitriles / pharmacology
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Optic Nerve Injuries / pathology
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Piperidines / pharmacology*
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Rats
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Retinal Ganglion Cells / drug effects*
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Retinal Ganglion Cells / pathology
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Scopolamine / pharmacology
Substances
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Benzopyrans
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Cholinergic Antagonists
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Cholinesterase Inhibitors
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Enzyme Inhibitors
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Indans
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Neuroprotective Agents
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Nitriles
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Piperidines
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ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate
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Glutamic Acid
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Mecamylamine
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Donepezil
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Scopolamine