a Department of Pediatrics , University of L'Aquila , L'Aquila , Italy.
b Child and Adolescent Neuropsychiatry, Medical School , University of Salerno , Salerno , Italy.
Expert Opin Investig Drugs. 2018 Dec;27(12):971-979. doi: 10.1080/13543784.2018.1543398. Epub 2018 Nov 13.
Epilepsy is a neurological disorder that significantly impacts the quality of life of affected persons. Despite advances in research, nearly a third of patients have refractory or pharmacoresistant epilepsy. Even though numerous antiepileptic drugs (AEDs) have been approved over the past decade, there are no agents that halt the development of epilepsy. Thus, new and improved AEDs to prevent these conditions are necessary.
We highlight recent advances in new and innovative drugs for epilepsy disorders. We review three small molecule drugs in phase II clinical trials: Cannabidivarin, BGG492 (Selurampanel) and Ganaloxone.
The full potential of Cannabidivarin will be realized by testing in other types of treatment-resistant seizures; if they are beneficial, larger phase III clinical trials would probably be undertaken in the same patient population. About BGG492, the challenge will be to find 'superselective' AMPAR antagonists targeting only calcium-permeable receptors, with specific mechanisms, that may be attractive partners for drugs in polytherapy. Moreover, there is anew interest surrounding Ganaloxone because of a new submicron formulation that improves its absorption and pharmacokinetic profile, but new studies are necessary before progressing. Further clinical innovations will define the future for these small molecule-type drugs in epilepsy therapeutics.
癫痫是一种严重影响患者生活质量的神经系统疾病。尽管研究取得了进展，但近三分之一的患者患有难治性或耐药性癫痫。尽管在过去十年中批准了许多抗癫痫药物（AEDs），但仍没有能够阻止癫痫发作的药物。因此，有必要开发新的、改进的 AED 来预防这些疾病。
我们重点介绍了癫痫疾病新的创新药物的最新进展。我们回顾了三种处于 II 期临床试验阶段的小分子药物：大麻二酚酸、BGG492（Selurampanel）和 Ganaloxone。
如果在其他类型的耐药性癫痫发作中进行测试，大麻二酚酸的全部潜力将得到体现；如果有效，可能会在同一患者群体中进行更大规模的 III 期临床试验。关于 BGG492，挑战将是找到针对仅具有特定机制的钙通透性受体的“超选择性”AMPA 拮抗剂，这可能是多疗法药物的有吸引力的合作伙伴。此外，由于新的亚微米制剂提高了其吸收和药代动力学特性，Ganaloxone 引起了新的关注，但在进一步发展之前需要进行新的研究。这些小分子类型药物在癫痫治疗中的未来将由进一步的临床创新来定义。
