Extransynaptic GABAA modulators for benzodiazepine refractory status epilepticus

癫痫持续状态（SE）是一个时间敏感的医疗紧急情况，经常成为

Status epilepticus (SE) is a time-sensitive medical emergency that often becomes refractory to current standard-of-care interventions. As seizures persist, medical treatments increase in severity from simple intravenous benzodiazepines (BZDs) administered within the first 15-30 minutes of SE, to anti-epileptic drugs after 30 minutes, to anesthetic and/or barbiturate induced coma. Treatment course beyond the initial BZDs is not clinically defined and the ability to stop SE even when treated in a timely manner is insufficient. Therefore, there exists a need for superior medical interventions for both rapid and delayed treatment of SE. We have identified a new compound that could fill this role. In preliminary testing, this compound was found to be far superior to BZDs in the treatment of nerve-agent induced SE. In this project we seek to determine if the compound may be efficacious in the treatment of SE induced by more standard chemoconvulsants that produce BZD-refractory SE. The second goal of the proposal is to determine the specific molecular target of this compound in live brain slices. Together, these data will help to support the development of this compound for potential use as a first-line treatment of SE, or second-line treatment of refractory SE, in human patients.