Flupirtine effectively prevents development of acute neonatal seizures in an animal model of global hypoxia

NEUROSCIENCE LETTERS

卷:607

Article

Sampath, Dayalan¹  Shmueli, Doron¹  White, Andrew M.¹  Raol, Yogendra H.¹ 

[1] Univ Colorado, Sch Med, Dept Pediat, Div Neurol,Translat Epilepsy Res Program, Aurora, CO 80045 USA

关键词: Neonatal seizures;    Video-EEG monitoring;    Hypoxia;    Flupirtine;    Potassium channel opener;   

DOI  :  10.1016/j.neulet.2015.09.005

来源: Elsevier

【 摘 要 】

Current first-line drugs for the treatment of neonatal seizures have limited efficacy and are associated with side effects. Uncontrolled seizures may exacerbate brain injury and contribute to later-life neurological disability. Therefore, it is critical to develop a treatment for neonatal seizures that is effective and safe. In early-life, when the gamma-aminobutyric acid (GABA) inhibitory system is not fully developed, potassium channels play an important role in controlling excitability. An earlier study demonstrated that flupirtine, a KCNQ potassium channel opener, is more efficacious than diazepam and phenobarbital for the treatment of chemoconvulsant-induced neonatal seizures. In newborns, seizures are most commonly associated with hypoxic-ischemic encephalopathy (HIE). Thus, in the present study, we examined the efficacy of flupirtine to treat neonatal seizures in an animal model of global hypoxia. Our results showed that flupirtine dose dependently blocks the occurrence of behavioral seizures in pups during hypoxia. Additionally, flupirtine inhibits the development of hypoxia-induced clinical seizures and associated epileptiform discharges, as well as purely electrographic (subclinical) seizures. These results suggest that flupirtine is an effective anti-seizure drug, and that further studies should be conducted to determine the time window within which it's administration can effectively treat neonatal seizures. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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