Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K.

Pharmacological reports : PR Pub Date : 2022-10-01 Epub Date: 2022-09-16 DOI:10.1007/s43440-022-00391-y

Isabel Vieira de Assis Lima, Hyorrana Priscila Pereira Pinto, Paula Maria Quaglio Bellozi, Maria Carolina Machado da Silva, Luciano R Vilela, Fabrício A Moreira, Márcio Flávio Dutra Moraes, Antônio Carlos Pinheiro de Oliveira

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引用次数: 1

Abstract

Background: The phytocannabinoid cannabidiol (CBD) has previously shown to have anticonvulsant effects in preclinical and clinical studies. Recently, CBD has been approved to treat certain types of drug-resistant epileptic syndromes. However, the underlying mechanism of action remains unclear. The phosphatidylinositol 3-kinase (PI3K) signaling pathway has been proposed to modulate seizures and might be recruited by CBD. Thus, we tested the hypothesis that the anticonvulsant effect of CBD involves PI3K in a seizure model induced by pentylenetetrazole (PTZ).

Methods: We employed pharmacological and genetic approaches to inhibit PI3K and quantified its effects on seizure duration, latency, and number.

Results: PI3K genetic ablation increased the duration and number of seizures. CBD inhibited PTZ-induced seizures in mice. Genetic deletion of PI3K or pretreatment with the selective inhibitor LY294002 prevented CBD effects.

Conclusion: Our data strengthen the hypothesis that the CBD anticonvulsant effect requires the PI3K signaling pathway.

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大麻二酚对戊四唑诱发癫痫发作的影响依赖于PI3K。

背景:植物大麻素大麻二酚(CBD)在临床前和临床研究中已显示出抗惊厥作用。最近，CBD已被批准用于治疗某些类型的耐药癫痫综合征。然而，其潜在的作用机制尚不清楚。磷脂酰肌醇3-激酶(PI3K)信号通路被认为可以调节癫痫发作，并可能被CBD招募。因此，我们在戊四唑(PTZ)诱导的癫痫发作模型中验证了CBD的抗惊厥作用涉及PI3K的假设。方法:采用药理学和遗传学方法抑制PI3K，并量化其对癫痫发作持续时间、潜伏期和次数的影响。结果:PI3K基因消融增加了癫痫发作的持续时间和次数。CBD抑制ptz诱导的小鼠癫痫发作。基因删除PI3K或用选择性抑制剂LY294002预处理可以阻止CBD的作用。结论:我们的数据加强了CBD抗惊厥作用需要PI3K信号通路的假设。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Pharmacological reports : PR

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