Effect of alpelisib, a selective phosphatidylinositol-3-kinase inhibitor, on seizure development in a rat pentylenetetrazole model

Abstract

Epilepsy is a neurological disease that results from an abnormality in the brain's activity. Phosphatidylinositol-3-kinase (PI3K) signaling pathway has played a crucial role in epilepsy pathogenesis. Alpelisib (ALP) is a selective inhibitor of PI3K. We examined the ability of ALP to treat pentylenetetrazole (PTZ)-induced convulsions in a rat model. Male Wistar rats (200-250 g, 8 weeks old) were injected intraperitoneally (IP) with ALP at different doses of 15 and 30 mg/kg, or vehicle 30 min prior to PTZ (70 mg/kg, IP) treatment. Racine's scale was used to assess behavioral seizures. The results showed that pretreatment with ALP decreased the seizure stages according to the Racine scale, significantly prolonged the duration of general tonic-clonic seizure (GTCS) and reduced the number of myoclonic jerks (P < 0.05). In conclusion, based on results it was shown that PI3K antagonist ALP inhibited PTZ-induced seizure by inhibiting the PI3K signaling pathway via ALP.