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


Published: Jan 18, 2024
Updated: 2024-01-18
Keywords:
Epilepsy Alpelisib Phosphatidylinositol-3-kinase Seizure Pentylenetetrazole
A Rostamkhani
N Mirazi
A Hosseini
https://orcid.org/0000-0002-1424-7843
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.

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