Preclinical efficacy of cannabidiol for the treatment of early-life seizures.
Preclinical efficacy of cannabidiol for the treatment of early-life seizures.
复制标题
大麻二酚治疗早期癫痫发作的临床前疗效。
DOI：
10.1007/s43440-022-00413-9
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Forcelli,PatrickA
中科院分区：
文献类型：
--
作者：
Witherspoon,Eric;Quinlan,Sean;Forcelli,PatrickA
背景早期癫痫的治疗是一个独特的挑战--一线治疗使许多人的癫痫发作控制不佳。针对目前一线抗癫痫药物(ASD)在生命早期的耐药性，出现了新的治疗方法。一种这样的疗法是大麻二醇(CBD)。虽然在成年癫痫模型中得到了很好的研究，但在未成熟动物中的研究却很少。方法对幼鼠给予CBD(1、10、50、100、200 mg/kg)进行预处理，并采用戊四氮(PTZ)和最大电休克(MES)两种成熟的抗癫痫筛选模型评价CBD的抗惊厥效果。结果在PTZ模型中，CBD延迟了青春期大鼠的癫痫发作，但不延迟新生大鼠的癫痫发作。相比之下，在MES模型中，较高剂量的CBD缩短了新生和青春期大鼠的癫痫发作持续时间。结论与年轻动物相比，老年动物的CBD效应增强，可产生年龄、模型和剂量依赖性的癫痫抑制。这些数据表明，新生儿癫痫(以P7治疗为模型)对CBD的反应可能较差。它们还表明，与部分运动性癫痫相比，强直性癫痫的疗效更好。
BackgroundThe treatment of epilepsy during early life poses unique challenges—first-line therapies leave many individuals with poorly controlled seizures. In response to the pharmaco-resistance of current first-line anti-seizure drugs (ASDs) during early life, new therapies have emerged. One such therapy is cannabidiol (CBD). While well studied in adult models of epilepsy, it is poorly studied in immature animals. Here we assessed the efficacy of CBD in immature rodent models of the epilepsies.MethodsPups were pre-treated with CBD (1, 10, 50, 100, 200 mg/kg) and assessed for anticonvulsant efficacy using two well-established anti-seizure screening models: the pentylenetetrazole (PTZ) and maximal electroshock (MES) models. We assessed drug efficacy in postnatal day (P)7 and P21 rats.ResultsIn the PTZ model, CBD delayed seizure onset in adolescent but not neonatal rats. By contrast, higher doses of CBD reduced seizure duration in both neonatal and adolescent rats in the MES model. The effects of CBD in both models were modest but consistent.ConclusionEfficacy of CBD increased in older as compared to younger animals, producing an age-, model-, and dose-dependent suppression of seizures. These data suggest neonatal seizures (modeled by P7 treatment) may be less responsive to CBD. They also suggest preferential efficacy against tonic seizures as compared to partial motor seizures.