Anticonvulsant activity of BmK AS, a sodium channel site 4-specific modulator
Anticonvulsant activity of BmK AS, a sodium channel site 4-specific modulator
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BmK AS（钠通道位点 4 特异性调节剂）的抗惊厥活性
DOI：
10.1016/j.yebeh.2010.12.006
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发表时间：
2011-02-01
影响因子：
2.6
通讯作者：
Ji, Yong-Hua
中科院分区：
文献类型：
--
作者：
Zhao, Rong;Weng, Chun-Chun;Ji, Yong-Hua
研究了从蝎毒中纯化的钠通道位点4选择性调节剂BmK AS对未麻醉大鼠急性戊四唑（PTZ）和匹罗卡平诱发癫痫发作的抗惊厥活性。在CA1区微注射生理盐水或BmK AS，然后在30分钟后给予致痫剂量的PTZ或匹罗卡品。评估BmK AS对PTZ或匹罗卡品诱发的癫痫样行为和皮质癫痫样脑电图活动的抗惊厥疗效。海马内注射BmK AS （0.05-1 μ g / 1 μ L）在PTZ模型中产生剂量依赖性抗惊厥活性，抑制癫痫发作相关行为，减少脑电图高振幅高频放电（HAFDs）的次数和持续时间。相比之下，在相同剂量范围内，BmK AS对匹罗卡平模型的癫痫样脑电图没有影响，尽管它确实增加了癫痫持续状态发作的潜伏期，并轻微但显著地降低了癫痫发作评分。总之，我们的研究结果表明，钠通道位点4选择性调节剂BmK AS是PTZ-的有效抑制剂，而不是匹罗卡品诱导的急性癫痫发作。这些结果表明，BmK AS可以作为探索不同钠通道亚型在癫痫发病中的作用的新探针，并可能成为开发专门用于治疗钠通道4位点相关癫痫的抗癫痫药物的潜在先导。(C) 2010爱思唯尔公司版权所有。
The anticonvulsant activity of BmK AS, a sodium channel site 4-selective modulator purified from scorpion venom (Buthus martensi Karsch), was investigated in unanesthetized rats with acute pentylenetetrazole (PTZ)- and pilocarpine-induced seizures. Rats were microinjected in the CA1 region with either saline or BmK AS, followed by epileptogenic doses of PTZ or pilocarpine 30 minutes later. The anticonvulsant efficacy of BmK AS in PTZ- or pilocarpine-evoked seizure-like behavior and cortical epileptiform EEG activity was assessed. Intrahippocampal injections of BmK AS (0.05-1 mu g in 1 mu L) produced dose-dependent anticonvulsant activity in the PTZ model, suppressing seizure-associated behavior and reducing both the number and duration of high-amplitude, high-frequency discharges (HAFDs) on the EEG. In contrast, BmK AS did not affect the epileptiform EEG in the pilocarpine model over the same dose range, although it did increase the latency to status epilepticus onset and slightly, but significantly, reduced the seizure score. In summary, our results demonstrate that the sodium channel site 4-selective modulator BmK AS is an effective inhibitor of PTZ- but not pilocarpine-induced acute seizures. These results indicate that BmK AS may serve as a novel probe in exploring the role of different sodium channel subtypes in an epileptogenic setting and as a potential lead in developing antiepileptic drugs specifically for the therapy of sodium channel site 4-related epilepsy. (C) 2010 Elsevier Inc. All rights reserved.