A KCNQ channel opener for experimental neonatal seizures and status epilepticus.
A KCNQ channel opener for experimental neonatal seizures and status epilepticus.
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DOI：
10.1002/ana.21593
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发表时间：
2009-03
影响因子：
11.2
通讯作者：
Cooper, Edward C.
中科院分区：
文献类型：
--
作者：
Raol, YogendraSinh H.;Lapides, David A.;Keating, Jeffery G.;Brooks-Kayal, Amy R.;Cooper, Edward C.
新生儿癫痫频繁发生，往往对抗惊厥药物无效，并与相当大的发病率和死亡率有关。遗传学和电生理学证据表明，KCNQ电压门控钾通道是新生儿大脑兴奋性的关键调节因子。这项研究验证了选择性开放KCNQ通道可能对治疗新生儿癫痫有效的假设。我们在出生后第10天用红藻氨酸或氟乙基诱发大鼠癫痫发作。我们使用量化的行为评分和皮层脑电图仪测量癫痫发作的活动性。我们比较了选择性KCNQ通道开放剂氟平与当前使用的两种药物苯巴比妥和安定治疗新生儿癫痫的疗效。与苯巴比妥或安定不同，氟平在海人酸前给药可防止动物出现癫痫状态(SE)。在氟乙基模型中，苯巴比妥和安定延长了癫痫发作的潜伏期，但氟平汀在整个实验过程中完全阻止了癫痫发作。当动物出现持续的红藻氨酸诱导的SE后，给药也能有效地阻止脑电和行为发作。氟平汀可引起剂量相关的镇静和抑制脑电活动，但不会导致呼吸抑制或导致任何死亡。在红藻氨酸和氟乙胺的症状性新生儿癫痫发作模型中，氟平似乎比两种常用的抗癫痫药物苯巴比妥和安定中的任何一种都更有效地预防和抑制癫痫发作。KCNQ通道开放剂值得进一步研究，作为婴儿和儿童癫痫的潜在治疗方法。
Neonatal seizures occur frequently, are often refractory to anticonvulsants, and are associated with considerable morbidity and mortality. Genetic and electrophysiological evidence indicates that KCNQ voltage-gated potassium channels are critical regulators of neonatal brain excitability. This study tests the hypothesis that selective openers of KCNQ channels may be effective for treatment of neonatal seizures. We induced seizures in postnatal day 10 rats with either kainic acid or flurothyl. We measured seizure activity using quantified behavioral rating and electrocorticography. We compared the efficacy of flupirtine, a selective KCNQ channel opener, with phenobarbital and diazepam, two drugs in current use for neonatal seizures. Unlike phenobarbital or diazepam, flupirtine prevented animals from developing status epilepticus (SE) when administered prior to kainate. In the flurothyl model, phenobarbital and diazepam increased latency to seizure onset, but flupirtine completely prevented seizures throughout the experiment. Flupirtine was also effective in arresting electrographic and behavioral seizures when administered after animals had developed continuous kainate-induced SE. Flupirtine caused dose-related sedation and suppressed EEG activity, but did not result in respiratory suppression or result in any mortality. Flupirtine appears more effective than either of two commonly used anti-epileptic drugs, phenobarbital and diazepam, in preventing and suppressing seizures in both the kainic acid and flurothyl models of symptomatic neonatal seizures. KCNQ channel openers merit further study as potential treatments for seizures in infants and children.
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影响因子：
5.3
作者：
McCabe, BK;Silveira, DC;Holmes, GL
通讯作者：
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影响因子：
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