Donepezil blocks voltage-gated ion channels in rat dissociated hippocampal neurons
文献类型：期刊论文
| 作者 | Yu, B; Hu, GY |
| 刊名 | EUROPEAN JOURNAL OF PHARMACOLOGY
 |
| 出版日期 | 2005-01-31 |
| 卷号 | 508期号:1-3页码:15-21 |
| 关键词 | Alzheimer's disease cholinesterase inhibitor Donepezil (E2020) Na+ channel K+ channel |
| ISSN号 | 0014-2999 |
| DOI | 10.1016/j.ejphar.2004.12.004 |
| 文献子类 | Article |
| 英文摘要 | Donepezil (E2020) is a novel cholinesterase inhibitor for the treatment of Alzheimer's disease. Recent studies show that it may act on targets other than acetylcliolinesterase in the brain. In the present study, the actions of donepezil on voltage-gated Na+ and K+ channels were investigated in rat dissociated hippocampal neurons. Donepezil reversibly inhibited voltage-activated Na+ current (I-Na), delayed rectifier K+ current (I-K) and fast transient K+ current (I-A). The inhibition of donepezil on I-Na was dependent on the holding potential. When neurons were held at -100, -80 and -60 mV, the IC50 value was 436 +/- 19, 291 +/- 26 and 3.8 +/- 0.3 muM, respectively. The drug did not affect the activation, fast inactivation of I-Na and its recovery from fast inactivation. The inhibition of donepezil on I-K (IC50=78 +/- 5 muM) was voltage-dependent, whereas that on I-A (IC50 = 249 +/- 25 muM) was voltage-in dependent. Donepezil caused a significant hyperpolarizing shift of the voltage-dependence of the activation and steady-state inactivation of I-K, without affecting the kinetic properties of I-A. Due to the high concentrations used, the blocking effects of donepezil on the voltage-gated ion channels are unlikely to contribute to the clinical benefits in patients with Alzheimer's disease. (C) 2004 Elsevier B.V. All rights reserved. |
| WOS关键词 | OXYGEN-GLUCOSE DEPRIVATION ; POTASSIUM CURRENT ; PYRAMIDAL NEURONS ; HUPERZINE-A ; GLUTAMATE NEUROTOXICITY ; DELAYED RECTIFIER ; CORTICAL-NEURONS ; INHIBITORS ; DISEASE ; CA1 |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000226894000003 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273936]  |
| 专题 | 药理学第二研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第一研究室 |
| 通讯作者 | Hu, GY |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yu, B,Hu, GY. Donepezil blocks voltage-gated ion channels in rat dissociated hippocampal neurons[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2005,508(1-3):15-21. |
| APA | Yu, B,&Hu, GY.(2005).Donepezil blocks voltage-gated ion channels in rat dissociated hippocampal neurons.EUROPEAN JOURNAL OF PHARMACOLOGY,508(1-3),15-21. |
| MLA | Yu, B,et al."Donepezil blocks voltage-gated ion channels in rat dissociated hippocampal neurons".EUROPEAN JOURNAL OF PHARMACOLOGY 508.1-3(2005):15-21. |
入库方式： OAI收割
来源：上海药物研究所
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