Valnoctamide enhances phasic inhibition: a potential target mechanism for the treatment of benzodiazepine-refractory status epilepticus.
Valnoctamide enhances phasic inhibition: a potential target mechanism for the treatment of benzodiazepine-refractory status epilepticus.
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Valnoctamide 增强阶段性抑制：治疗苯二氮卓类难治性癫痫持续状态的潜在目标机制。
DOI：
10.1111/epi.12702
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发表时间：
2014
期刊：
影响因子：
5.6
通讯作者：
Dudek,FEdward
中科院分区：
文献类型：
--
作者：
Spampanato,Jay;Dudek,FEdward
丙戊酸盐的衍生物--戊酸钠（VCD）可抑制癫痫持续状态（SE）动物模型中的电描记癫痫发作，即使癫痫发作对苯二氮卓类药物（BZD）耐药。因此，我们测试了VCD对CA 1锥体细胞中微型抑制性突触后电流（mIPSC）的影响，以确定VCD是否直接作用于γ-氨基丁酸（GABA）A受体。浴用VCD诱导mIPSC衰变的特异性、快速、剂量依赖性和可逆性减缓（即，增加的时间常数），而对它们的频率或幅度没有影响。这与BZD对mIPSC的作用相似，但VCD的作用在存在BZD结合位点拮抗剂氟马西尼的情况下持续存在，并且与BZD地西泮的作用相加。这些数据表明，VCD通过与BZD不同的结合位点发挥作用，这可能是其对BZD难治性SE的影响。总结本文的PowerPoint幻灯片可在此处的支持信息部分下载。
Valnoctamide (VCD), a derivative of valproate, suppresses electrographic seizures in animal models of status epilepticus (SE), even when the seizures are resistant to benzodiazepines (BZDs). We therefore tested the effect of VCD on miniature inhibitory postsynaptic currents (mIPSCs) in CA1 pyramidal cells to determine if VCD acts directly on γ‐aminobutyric acid (GABA)Areceptors. Bath‐applied VCD induced a specific, rapid, dose‐dependent, and reversible slowing of the decay of mIPSCs (i.e., increased time constant) with no effect on their frequency or amplitude. This is similar to the effect of BZDs on mIPSCs, but the effect of VCD persisted in the presence of the BZD‐binding site antagonist flumazenil, and was additive to the effect of the BZD, diazepam. These data suggest that VCD acts through a different binding site than that of BZDs, which likely accounts for its effect on BZD‐refractory SE.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.