Department of Neurology, Baylor College of Medicine, Houston, Texas, USA.
Department of Neurology, American University of Beirut medical Center, Beirut, Lebanon.
Muscle Nerve. 2021 Oct;64(4):504-508. doi: 10.1002/mus.27385. Epub 2021 Aug 21.
INTRODUCTION/AIMS: Perampanel, a selective noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist, is capable of slowing the progression of the amyotrophic lateral sclerosis (ALS) phenotype and increasing the number of anterior horn cells in transgenic mice. Trials of perampanel in epilepsy showed a favorable tolerability profile. In this study we aimed to determine the tolerability and safety of perampanel in patients with ALS.
Enrolled subjects were started on 2 mg/day of perampanel and the dose was increased by 2 mg/day every week to a maximum dose of 8 mg/day. Our primary outcome measure was tolerability, which was evaluated by monitoring adverse events. The secondary outcome measure was clinical progression, assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) and spirometry.
Six participants were enrolled. All had adverse events, mostly behavioral. Two completed the trial and the other four withdrew due to adverse events. All participants reported resolution of these events after discontinuation of the drug. The trial was halted due to the large number of adverse events.
The use of perampanel in this study of ALS was limited by its poor tolerability.
介绍/目的：吡仑帕奈是一种选择性非竞争性 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）拮抗剂，能够减缓肌萎缩侧索硬化症（ALS）表型的进展，并增加转基因小鼠前角细胞的数量。吡仑帕奈在癫痫中的试验显示出良好的耐受性。在这项研究中，我们旨在确定吡仑帕奈在 ALS 患者中的耐受性和安全性。
入组患者开始服用 2mg/天的吡仑帕奈，每周增加 2mg/天，最大剂量为 8mg/天。我们的主要观察指标是耐受性，通过监测不良事件进行评估。次要观察指标是临床进展，使用肌萎缩侧索硬化功能评定量表修订版（ALSFRS-R）和肺活量计进行评估。
共入组 6 名参与者。所有人都有不良事件，主要是行为相关的。其中 2 人完成了试验，另外 4 人因不良事件退出。所有参与者在停药后均报告了这些事件的解决。由于不良事件数量众多，试验被中止。
吡仑帕奈在这项 ALS 研究中的使用受到其较差耐受性的限制。
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