Monica Garcia-Durillo and Bruno. G. Frenguelli  

Approximately 30% of patients with status epilepticus (SE) become refractory to two or more antiseizure medications (ASM). There is thus a real need to identify novel targets to develop new ASMs for treating this clinical emergency. This study evaluated the effect of the selective P2X7R antagonist A740003 on acute seizures in the dentate gyrus (DG) of hippocampal brain slices, where P2X7Rs are highly expressed, with a view to establishing its potential use as a therapy or adjunct with lorazepam (LZP) in refractory SE.. Our study revealed that, in the absence of changes in mRNA for P2X7Rs or inflammatory markers, P2X7R antagonism did not alter the frequency of SLEs. However, A740003 in conjunction with LZP delayed the onset of seizures. Furthermore, our results support the need for employing LZP before seizures become refractory during SE (i.e., in the 60 min frame since first seizure appears) as delayed of application LZP increased seizure frequency. These studies reveal possible sites of intervention that could have a positive impact in patients with high risk of suffering SE or its drug-refractory variant.

Neuropharmacology. July 2023