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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 .

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