Electrocorticography demonstrates beneficial effects of EP-80317 in a model of status epilepticus

Status epilepticus (SE) is a serious life-threatening condition. Treatment of SE is based on a stage approach, going from benzodiazepines in the early stage to intensive care unit and general anesthesia in severe stages. Treatment of SE is frequently unsuccessful, and high levels of mortality and morbidity are reported. Several risk factors for SE occurrence and recurrence have been identified, making prevention of this condition a primary objective. EP-80317, a ghrelin receptor antagonist, displays anticonvulsant properties on behavioral convulsive episodes. In this study, we have characterized the ability of EP-80317 to prevent progression from non-convulsive to convulsive seizures and to SE in the pilocarpine model by video-electrocorticography. SE developed in 100% of rats pretreated with saline, but only in 50% of those pretreated with EP-80317. Seizures were similarly evoked in both groups, but different rates of convulsive vs. non-convulsive episodes were observed. In particular, the rate of convulsive seizures was 15% in EP-80317-pretreated rats that did not experience SE (EP-80317/Non-SE), whereas it was about 75% in saline-pretreated group and in EP-80317-pretreated rats that experienced SE (EP-80317/SE). Moreover, after pilocarpine administration, saline-pretreated and EP-80317/SE rats showed a worsening in behavioral manifestation and seizure duration, and a progression of the power spectrum of convulsive seizures. This progressive worsening was not observed in EP-80317/Non-SE rats. We report for the first time that EP-80317 prevents the progression from non-convulsive to convulsive seizures and to SE in pilocarpine-treated rats.