ArticleNeuropharmacology2017
Anticonvulsant effect of flupirtine in an animal model of neonatal hypoxic-ischemic encephalopathy.
Article in Neuropharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Alternative Targets for Modulators of Mitochondrial Potassium Channels.Molecules (Basel, Switzerland) · 2022Review
- Novel Therapeutics for Neonatal Seizures.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Continuous Video Electroencephalogram during Hypoxia-Ischemia in Neonatal Mice.Journal of visualized experiments : JoVE · 2020Article
- Functional responses of the hippocampus to hyperexcitability depend on directed, neuron-specific KCNQ2 KHippocampus · 2020Article
- Electroencephalogram studies of hypoxic ischemia in fetal and neonatal animal models.Neural regeneration research · 2020Review
- Neuronal Circuit Activity during Neonatal Hypoxic-Ischemic Seizures in Mice.Annals of neurology · 2019Article
- Sex-Dependent Signaling Pathways Underlying Seizure Susceptibility and the Role of Chloride Cotransporters.Cells · 2019Review
- Flupirtine Analogues: Explorative Synthesis and Influence of Chemical Structure on KChemistryOpen · 2019Article
- Brain Distribution and Metabolism of Flupirtine, a Nonopioid Analgesic Drug with Antiseizure Effects, in Neonatal Rats.Pharmaceutics · 2018Article
- A Model of Perinatal Ischemic Stroke in the Rat: 20 Years Already and What Lessons?Frontiers in neurology · 2018Review
- Flupirtine and diazepam combination terminates established status epilepticus: results in three rodent models.Annals of clinical and translational neurology · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Research studies suggest that neonatal seizures, which are most commonly associated with hypoxic-ischemic injury, may contribute to brain injury and adverse neurologic outcome. Unfortunately, neonatal seizures are often resistant to treatment with current anticonvulsants. In the present study, we evaluated the efficacy of flupirtine, administered at clinically relevant time-points, for the treatment of neonatal seizures in an animal model of hypoxic-ischemic injury that closely replicates features of the human syndrome. We also compared the efficacy of flupirtine to that of phenobarbital, the current first-line drug for neonatal seizures. Flupirtine is a KCNQ potassium channel opener. KCNQ channels play an important role in controlling brain excitability during early development. In this study, hypoxic-ischemic injury was induced in neonatal rats, and synchronized video-EEG records were acquired at various time-points during the experiment to identify seizures. The results revealed that flupirtine, administered either 5 min after the first electroclinical seizure, or following completion of 2 h of hypoxia, i.e., during the immediate reperfusion period, reduced the number of rats with electroclinical seizures, and also the frequency and total duration of electroclinical seizures. Further, daily dosing of flupirtine decreased the seizure burden over 3 days following HI-induction, and modified the natural evolution of acute seizures. Moreover, compared to a therapeutic dose of phenobarbital, which was modestly effective against electroclinical seizures, flupirtine showed greater efficacy. Our results indicate that flupirtine is an extremely effective treatment for neonatal seizures in rats and provide evidence for a trial of this medication in newborn humans.
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