title: Flupirtine effectively prevents development of acute neonatal seizures in an animal model of global hypoxia.
abstract: 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 γ-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.
authors.affiliation: Department of Pediatrics, Division of Neurology, School of Medicine, Translational Epilepsy Research Program, University of Colorado, School of Medicine, Aurora, CO 80045, United States.
authors.forename: Dayalan
authors.initials: D
authors.lastname: Sampath
authors.affiliation: Department of Pediatrics, Division of Neurology, School of Medicine, Translational Epilepsy Research Program, University of Colorado, School of Medicine, Aurora, CO 80045, United States.
authors.forename: Doron
authors.initials: D
authors.lastname: Shmueli
authors.affiliation: Department of Pediatrics, Division of Neurology, School of Medicine, Translational Epilepsy Research Program, University of Colorado, School of Medicine, Aurora, CO 80045, United States.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: White
authors.affiliation: Department of Pediatrics, Division of Neurology, School of Medicine, Translational Epilepsy Research Program, University of Colorado, School of Medicine, Aurora, CO 80045, United States. Electronic address: Yogendra.Raol@ucdenver.edu.
authors.forename: Yogendra H
authors.initials: YH
authors.lastname: Raol
mesh_terms: D000208:Acute Disease; D000631:Aminopyridines / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use*; D005260:Female; D000860:Hypoxia / Q000150:complications*; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D008297:Male; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000631:Aminopyridines; D000927:Anticonvulsants; D051656:KCNQ Potassium Channels; C034161:flupirtine
keywords: Flupirtine; Hypoxia; Neonatal seizures; Potassium channel opener; Video-EEG monitoring