Inhibition of calcium-permeable and calcium-impermeable AMPA receptors by perampanel in rat brain neurons
Inhibition of calcium-permeable and calcium-impermeable AMPA receptors by perampanel in rat brain neurons
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DOI：
10.1016/j.neulet.2016.09.028
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发表时间：
2016-10-28
影响因子：
2.5
通讯作者：
Barygin, Oleg I.
中科院分区：
文献类型：
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作者：
Barygin, Oleg I.
Perampanel是一种抗癫痫药物，用于治疗部分性发作和全身强直阵挛性发作。它是一种高选择性AMPA受体变构拮抗剂。然而，不同研究中已发表的perampanel活性数据各不相同。在本研究中，我们使用全细胞膜片钳技术研究了perampanel对大鼠脑神经元中天然钙渗透性和钙非渗透性AMPA受体的抑制作用。我们发现，大鼠巨大纹状体中间神经元的钙渗透性AMPA受体和海马CA 1锥体神经元的钙非渗透性受体之间perampanel作用的抑制活性和动力学没有差异（IC 50值约为60 nM）。此外，perampanel对红藻氨酸盐和谷氨酸盐诱导的稳态电流产生了相同的抑制作用。另一方面，在存在环噻嗪的情况下，perampanel诱导的抑制作用显著降低（IC 50值增加至1.2 +/- 0.2 μ M）。我们证明perampanel与GYKI-52466竞争结合位点。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Perampanel is an antiepileptic drug that is used to treat partial -onset seizures and generalized tonicclonic seizures. It is a highly selective AMPA receptor allosteric antagonist. However, published data on perampanel activity vary in different studies. In the present work we studied the inhibition of native calcium -permeable and calcium-impermeable AMPA receptors in rat brain neurons by perampanel using whole-cell patch clamp technique. We found that inhibitory activity and kinetics of perampanel action do not differ between calcium-permeable AMPA receptors of rat giant striatum interneurons and calcium-impermeable receptors of hippocampal CA1 pyramidal neurons (the IC50 value about 60 nM). Also, perampanel caused the same inhibition of steady-state currents induced by kainate and glutamate. From the other side perampanel-induced inhibition was markedly reduced in the presence of cyclothiazide (IC50 value increased to 1.2 +/- 0.2 mu M). We demonstrated that perampanel competes with GYKI-52466 for binding site. (C) 2016 Elsevier Ireland Ltd. All rights reserved.