کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9921516 | 1559226 | 2005 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Donepezil blocks voltage-gated ion channels in rat dissociated hippocampal neurons
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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 acetylcholinesterase 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 (INa), delayed rectifier K+ current (IK) and fast transient K+ current (IA). The inhibition of donepezil on INa was dependent on the holding potential. When neurons were held at â100, â80 and â60 mV, the IC50 value was 436±19, 291±26 and 3.8±0.3 μM, respectively. The drug did not affect the activation, fast inactivation of INa and its recovery from fast inactivation. The inhibition of donepezil on IK (IC50=78±5 μM) was voltage-dependent, whereas that on IA (IC50=249±25 μM) was voltage-independent. Donepezil caused a significant hyperpolarizing shift of the voltage-dependence of the activation and steady-state inactivation of IK, without affecting the kinetic properties of IA. 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 508, Issues 1â3, 31 January 2005, Pages 15-21
Journal: European Journal of Pharmacology - Volume 508, Issues 1â3, 31 January 2005, Pages 15-21
نویسندگان
Bo Yu, Guo-Yuan Hu,