Fanapanel

Exposure to organophosphorus nerve agents (OPNAs) like soman frequently develops status epilepticus (SE), leading to brain damage. Existing antiseizure medications (e.g., diazepam, DZP) often demonstrate insufficient efficacy. To develop more effective treatments for OPNA-induced seizures, this study evaluated the efficacy of glutamate receptor antagonists with distinct mechanisms of action in a soman-induced rat seizure model. After 5 min of subcutaneous exposure to 110 μg/kg soman, which induced SE, rats received intraperitoneal injections (10 mg/kg) of perampanel (PER), fanapanel (FNP), IEM-1925 (IEM), or DZP. The results showed that IEM significantly suppressed seizure activity and improved survival. The survival rate of the vehicle-treated control group was 31.25 %, whereas DZP, FNP, and IEM increased survival rates to 50 %, 43.75 %, and 56.25 % respectively. Electroencephalographic (EEG) recordings for 24 h indicated that both DZP and IEM controlled soman-induced SE. However, while DZP initially blocked the onset of seizures, they recurred after its transient anticonvulsant effect wore off. In contrast, IEM reduced behavioral convulsion intensity and total duration of SE. Histopathological examinations (HE, Nissl, immunohistochemistry, and immunofluorescence) showed that IEM attenuated hippocampal CA1, CA2, and DG neuronal damage. Behavioral tests (open field, novel object recognition, and Y maze) confirmed IEM outperformed DZP and the solvent-treated group in ameliorating soman-induced anxiety, cognitive dysfunction, and memory impairment. In conclusion, IEM demonstrates potent triple effects-antiseizure, neuroprotective, and cognitive improving in soman exposure model, providing a novel therapeutic strategy and candidate drug for the medical treatment of OPNAs poisoning.