Small-molecule caspase-1 inhibitor CZL80 terminates refractory status epilepticus via inhibition of glutamatergic transmission

• Published in: Acta pharmacologica Sinica Vol. 45; no. 7; pp. 1381 - 1392
• Main Authors: Wang, Fei, Wang, Yu, Zhang, Qing-yang, Hu, Ke-yu, Song, Ying-jie, Yang, Lin, Fei, Fan, Xu, Ceng-lin, Cui, Sun-liang, Ruan, Ye-ping, Wang, Yi, Chen, Zhong
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.07.2024; Nature Publishing Group
• Subjects: Acids; Animals; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Biomedical and Life Sciences; Biomedicine; Caspase 1 - metabolism; Caspase Inhibitors - pharmacology; Caspase Inhibitors - therapeutic use; Caspase-1; Convulsions & seizures; Cytokines; Diazepam; Diazepam - pharmacology; Diazepam - therapeutic use; Drug resistance; Epilepsy; Glutamatergic transmission; Glutamic Acid - metabolism; Immunology; Internal Medicine; Kainic acid; Kainic Acid - pharmacology; Laboratory animals; Life sciences; Male; Medical Microbiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurosciences; Peptides; Pharmaceutical sciences; Pharmacology/Toxicology; Photometry; Pilocarpine; Seizures; Status Epilepticus - drug therapy; Synaptic Transmission - drug effects; Vaccine; status epilepticus; caspase-1 inhibitor; therapeutic time window; diazepam; glutamatergic synaptic transmission

Status epilepticus (SE), a serious and often life-threatening medical emergency, is characterized by abnormally prolonged seizures. It is not effectively managed by present first-line anti-seizure medications and could readily develop into drug resistance without timely treatment. In this study, we...