Effect of Duvelisib, a Selective PI3K Inhibitor on Seizure Activity in Pentylenetetrazole-Induced Convulsions Animal Model.

IF 2.9 Q2 NEUROSCIENCES Neuroscience Insights Pub Date : 2023-09-14 eCollection Date: 2023-01-01 DOI:10.1177/26331055231198013

Mahnaz Abdolrahmani, Naser Mirazi, Abdolkarim Hosseini

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Abstract

Epilepsy is one of the most common neurological diseases, which is caused by abnormal brain activity. A wide variety of studies have shown the importance of the phosphatidylinositol-3-kinase (PI3K) signaling pathway in epilepsy pathogenesis. Duvelisib (DUV) is a selective inhibitor of PI3K. The present study investigated the anticonvulsant potential of DUV in a rat model of pentylenetetrazole (PTZ)-induced convulsions. Male Wistar rats (200-250 g, 8 weeks old) were injected intraperitoneally (IP) with DUV at different doses of 5 and 10 mg/kg, or vehicle 30 minutes prior to PTZ (70 mg/kg, IP) treatment. Based on Racine’s scale, behavioral seizures were assessed. The results showed that pretreatment with DUV prolonged the seizure stages according to the Racine scale, significantly decreased the duration of general tonic-clonic seizure and reduced the number of myoclonic jerks (P < .05). In conclusion, we found that PI3K antagonist DUV significantly reduced PTZ-induced seizures, indicating that DUV exerts an anticonvulsant effect by inhibiting PI3K signaling pathway.

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选择性PI3K抑制剂Duvelisib对戊四唑诱导的惊厥动物模型癫痫发作活性的影响。

癫痫是最常见的神经系统疾病之一，由大脑活动异常引起。多种研究表明磷脂酰肌醇-3-激酶（PI3K）信号通路在癫痫发病机制中的重要性。Duvelisib（DUV）是PI3K的选择性抑制剂。本研究在戊四唑（PTZ）诱导的大鼠惊厥模型中研究了DUV的抗惊厥潜力。雄性Wistar大鼠（200-250 g、 8 周龄）腹膜内注射DUV，剂量分别为5和10 mg/kg，或车辆30 PTZ前几分钟（70 mg/kg、IP）处理。根据拉辛量表，对行为性癫痫进行评估。结果表明，DUV预处理延长了Racine量表的发作期，显著缩短了全身强直阵挛发作的持续时间，减少了肌阵挛抽搐的次数（P

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