Open AccessFlupirtine and diazepam combination terminates established status epilepticus: results in three rodent models
Author(s) -
Zhang Terry,
Todorovic Marko S.,
Williamson John,
Kapur Jaideep
Publication year - 2017
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.497
Subject(s) - diazepam , status epilepticus , medicine , benzodiazepine , potassium channel opener , hippocampus , pharmacology , anesthesia , pilocarpine , epilepsy , potassium channel , psychiatry , receptor
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 .