論文 - 詳細
| RRC ID | 2760 |
|---|---|
| 著者 | Akasofu S, Kimura M, Kosasa T, Ogura H, Sawada K. |
| タイトル | Protective effect of donepezil in primary-cultured rat cortical neurons exposed to N-methyl-d-aspartate (NMDA) toxicity. |
| ジャーナル | Eur J Pharmacol |
| Abstract |
Donepezil has a neuroprotective effect against oxygen-glucose deprivation injury and glutamate toxicity in cultured cortical neurons. In this study, we further characterized the neuroprotective properties of donepezil in rat cortical cell cultures using glutamate receptor-specific agonists (N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and kainate). Pretreatment with donepezil (1 microM) for 12 h significantly decreased the lactate dehydrogenase (LDH) release in response to NMDA (100 microM) by 43.8%, and reduced the LDH release in response to kainate (100 microM) and AMPA (100 microM) by 11.9% and 7.5% (without statistical significance), respectively. Donepezil appeared to inhibit LDH release in a concentration-dependent manner at 0.1-10 microM. Cortical neurons exposed to NMDA retained a normal morphological appearance in the presence of 10 microM donepezil. In binding assay for glutamate receptors, donepezil at 100 microM only slightly inhibited binding to the glycine and polyamine sites on NMDA receptor complex. On the other hand, 12 h pretreatment with donepezil at 10 and 100 microM significantly decreased the NMDA-induced increase of intracellular calcium concentration ([Ca2+]i). In conclusion, our results show that donepezil has protective activity against NMDA toxicity in cortical neurons, and this neuroprotection seems to be partially mediated by inhibition of the increase of [Ca2+]i. |
| 巻・号 | 530(3) |
| ページ | 215-22 |
| 公開日 | 2006-1-20 |
| DOI | 10.1016/j.ejphar.2005.11.057 |
| PII | S0014-2999(05)01272-0 |
| PMID | 16406045 |
| MeSH | Animals Calcium / metabolism Cells, Cultured Cerebral Cortex / cytology Cerebral Cortex / embryology Cholinesterase Inhibitors / pharmacology Donepezil Indans / pharmacology* Kainic Acid / toxicity L-Lactate Dehydrogenase / metabolism N-Methylaspartate / toxicity* Neurons / drug effects* Neurons / metabolism Neurons / pathology Neuroprotective Agents / pharmacology* Nootropic Agents / pharmacology Piperidines / pharmacology* Rats Rats, Wistar Receptors, Glutamate / metabolism alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / toxicity |
| IF | 3.263 |
| 引用数 | 29 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
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オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
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