Abstract:
Antiseizure medications are the cornerstone pharmacotherapy for epilepsy. They are not devoid of side effects. In search for better-tolerated antiseizure agents, cannabinoid compounds and other N-acylethanolamines not directly binding cannabinoid receptors have drawn significant attention. Among these, palmitoylethanolamide (PEA) has shown neuroprotective, anti-inflammatory, and analgesic properties. All studies examining PEA\'s role in epilepsy and acute seizures were systematically reviewed. Preclinical studies indicated a systematically reduced PEA tone accompanied by alterations of endocannabinoid levels. PEA supplementation reduced seizure frequency and severity in animal models of epilepsy and acute seizures, in some cases, similarly to available antiseizure medications but with a better safety profile. The peripheral-brain immune system seemed to be more effectively modulated by subchronic pretreatment with PEA, with positive consequences in terms of better responding to subsequent epileptogenic insults. PEA treatment restored the endocannabinoid level changes that occur in a seizure episode, with potential preventive implications in terms of neural damage. Neurobiological mechanisms for PEA antiseizure effect seemed to include the activation of the endocannabinoid system and the modulation of neuroinflammation and excitotoxicity. Although no human study was identified, there is ground for testing the antiseizure potential of PEA and its safety profile in human studies of epilepsy.
摘要:
抗癫痫药物是癫痫的基础药物治疗。它们并非没有副作用。为了寻找耐受性更好的抗癫痫药,不直接结合大麻素受体的大麻素化合物和其他N-酰基乙醇胺已经引起了极大的关注。其中,棕榈酰乙醇胺(PEA)具有神经保护作用,抗炎,和镇痛性能。系统回顾了所有研究PEA在癫痫和急性癫痫发作中的作用。临床前研究表明,PEA音调系统性降低,并伴有内源性大麻素水平的改变。补充PEA可降低癫痫和急性发作动物模型中的癫痫发作频率和严重程度,在某些情况下,与现有的抗癫痫药物相似,但安全性更好。PEA亚慢性预处理似乎更有效地调节了周围脑免疫系统,在更好地应对随后的癫痫发作方面具有积极的后果。PEA治疗恢复了癫痫发作中发生的内源性大麻素水平变化,在神经损伤方面具有潜在的预防意义。PEA抗癫痫作用的神经生物学机制似乎包括内源性大麻素系统的激活以及神经炎症和兴奋性毒性的调节。虽然没有人类研究,在人类癫痫研究中,有理由测试PEA的抗癫痫潜力及其安全性。