Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Ther Clin Risk Manag. 2013;9:285-93. doi: 10.2147/TCRM.S37317. Epub 2013 Jul 8.
Perampanel (2-[2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl] benzonitrile hydrate) is the latest in the line of new antiepileptic drugs with a novel mechanism of action. Perampanel inhibits α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-induced increases in intracellular Ca(2+) and selectively blocks AMPA receptor-mediated synaptic transmission, thus reducing neuronal excitation. Three Phase III multicenter, randomized, double-blind, placebo-controlled trials demonstrated the efficacy and good tolerability of perampanel as adjunctive treatment in patients with refractory partial-onset seizures. The drug is approved for use in the European Union and United States, with expected release onto the American market in June-September 2013, pending US Drug Enforcement Agency classification. The pharmacology of perampanel offers potential as more than just another new antiepileptic drug. This first-in-class drug will provide another option for practitioners of rational polytherapy. As an AMPA-receptor antagonist, perampanel may possess antiepileptogenic properties in addition to its demonstrated antiseizure properties.
吡仑帕奈(2-[2-氧代-1-苯基-5-吡啶-2-基-1,2-二氢吡啶-3-基]苯甲腈水合物)是作用机制新颖的新一代抗癫痫药物之一。吡仑帕奈抑制α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)诱导的细胞内 Ca(2+)增加,并选择性阻断 AMPA 受体介导的突触传递,从而减少神经元兴奋。三项 III 期多中心、随机、双盲、安慰剂对照试验证明了吡仑帕奈作为辅助治疗难治性部分发作性癫痫的疗效和良好耐受性。该药已在欧盟和美国获得批准使用,预计将于 2013 年 6 月至 9 月在美国市场上市,等待美国缉毒局的分类。吡仑帕奈的药理学不仅提供了另一种新型抗癫痫药物的潜力。这种首创药物将为合理联合治疗的从业者提供另一种选择。作为 AMPA 受体拮抗剂,吡仑帕奈除了已证明的抗惊厥作用外,可能还具有抗癫痫发生的特性。