Flupirtine and diazepam combination terminates established status epilepticus: results in three rodent models

Terry Zhang, Marko S. Todorovic, John Williamson, Jaideep Kapur

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Objective: Status epilepticus (SE) is a neurological emergency requiring rapid termination of seizures. New treatment choices are needed for benzodiazepine-refractory SE or established SE (ESE). Previous studies have demonstrated that the potassium-channel opener flupirtine terminates seizures in neonatal animals. However, its effectiveness in adult ESE has not been tested. We tested whether flupirtine alone or in combination with the benzodiazepine diazepam would terminate ESE in three animal models. Methods: SE was induced by administration of lithium followed by pilocarpine, by electrical stimulation of the hippocampus or by diisopropylfluorophosphate (DFP) administration. Seizures were assessed by EEG recorded from the hippocampus and cortex. Results: Flupirtine alone did not terminate ESE within 60 min of administration in any of the three models of ESE. A combination of flupirtine and diazepam terminated ESE within 60 min in all the three models. The drug combination shortened the duration of ESE in all three models. Drug responsiveness was distinct between each model. Conclusion: A combination of the potassium channel opener flupirtine and diazepam is a potential therapy for ESE.

Original languageEnglish
Pages (from-to)888-896
Number of pages9
JournalAnnals of Clinical and Translational Neurology
Volume4
Issue number12
DOIs
StatePublished - Dec 2017
Externally publishedYes

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