Institute of Pharmacology, Toxicology and Pharmacy, Ludwig-Maximilians-University (LMU), Munich, Germany.
Department of Neurology, Christian Doppler Klinik, University Hospital Paracelsus Medical University, Salzburg, Austria.
Epilepsia. 2019 Mar;60 Suppl 1:22-36. doi: 10.1111/epi.14456. Epub 2018 Jun 28.
This article reviews the profile of perampanel, a novel noncompetitive α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist, and its role as a potential broad-spectrum antiepileptic drug in the treatment of epilepsy. For this narrative review, data were collected using specified search criteria. Articles reporting the evidence for perampanel's efficacy from preclinical models, phase 3 clinical studies, observational studies, and descriptive evidence were included. AMPA receptors play a key role in mediating the action of glutamate at the excitatory synapse. Preclinical research showed the AMPA receptor blockade to constitute a promising target for antiepileptic drug therapy. In animal models, perampanel proved to be protective against seizures and reduce seizure severity and duration. Four phase-3 randomized controlled trials (3 in patients with focal seizures and one in primary generalized tonic-clonic seizures in idiopathic generalized epilepsy) have been completed. In focal (partial) onset seizures, perampanel (4, 8, and 12 mg) significantly reduced seizure frequency per 28 days (23.3%-28.8% vs 12.8%; P < .01) and responder rates (≥50% reduction in seizures) (28.5%-35.3% vs 19.3%; P < .05) compared with placebo. In primary generalized tonic-clonic seizures, perampanel 8 mg resulted in greater reduction in seizure frequency per 28 days (-76.5% vs -38.4%; P < .0001) and responder rate (64.2% vs 39.5%; P = .0019) than placebo. The efficacy, safety, and tolerability of perampanel have been reproduced in real-world clinical practice, and the agent has been shown to be effective in other epilepsy syndromes. Perampanel is a potentially broad-spectrum antiepileptic drug with a novel mechanism of action that may be a useful addition for patients with epilepsy with various seizure types. The availability of novel antiepileptic drugs for epilepsy treatment enables more individualized treatment for these patients.
这篇文章回顾了吡仑帕奈的概况，吡仑帕奈是一种新型的非竞争性α-氨基-3-羟甲基-4-异恶唑丙酸（AMPA）受体拮抗剂，作为一种治疗癫痫的潜在广谱抗癫痫药物。为了进行这次叙述性综述，我们使用了特定的搜索标准来收集数据。我们纳入了报告吡仑帕奈在临床前模型、3 期临床试验、观察性研究和描述性证据中的疗效的文章。AMPA 受体在介导谷氨酸在兴奋性突触中的作用方面发挥着关键作用。临床前研究表明，AMPA 受体阻断可能是抗癫痫治疗的一个有希望的靶点。在动物模型中，吡仑帕奈已被证明可预防癫痫发作，并降低癫痫发作的严重程度和持续时间。四项 3 期随机对照试验（3 项针对局灶性发作，1 项针对特发性全面性癫痫强直-阵挛发作）已经完成。在局灶性（部分）发作性癫痫中，吡仑帕奈（4、8 和 12 mg）可显著降低 28 天的癫痫发作频率（23.3%-28.8%比 12.8%；P <.01）和应答率（癫痫发作减少≥50%）（28.5%-35.3%比 19.3%；P <.05），与安慰剂相比。在原发性全面性强直-阵挛发作中，吡仑帕奈 8 mg 可使 28 天的癫痫发作频率降低（-76.5%比-38.4%；P <.0001）和应答率（64.2%比 39.5%；P =.0019）高于安慰剂。吡仑帕奈在真实世界的临床实践中的疗效、安全性和耐受性已经得到复制，并且该药物已被证明在其他癫痫综合征中有效。吡仑帕奈是一种具有新型作用机制的潜在广谱抗癫痫药物，可能对各种癫痫发作类型的癫痫患者有益。新型抗癫痫药物的出现为这些患者提供了更个性化的治疗选择。
