Unit of Neurology, Department of Medicine, Florence Health Authority, Firenze, Italy.
Expert Rev Neurother. 2013 Jun;13(6):647-55. doi: 10.1586/ern.13.46.
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the postsynaptic membrane are involved in fast excitatory signaling in the brain and their activation may lead to the firing of action potentials. Talampanel and perampanel were the first noncompetitive AMPA receptor antagonists to be tested as add-on drugs in patients with refractory partial seizures, and were found to be effective in improving seizure control. Due to an unfavorable kinetic and tolerability profile, talampanel clinical development in the field of epilepsy was discontinued early while perampanel has been recently approved in Europe and the USA as adjunctive therapy for adults with partial seizures with or without secondary generalization. The recommended perampanel starting dose is 2 mg/day once daily, which can be increased up to the recommended maintenance dose of 4-8 mg/day. Increments should be of 2 mg/day and based on clinical response and tolerability. Titration should be performed at 1-week intervals or at lower speed and a 12-mg daily dose should be considered after careful evaluation. To date, no serious and/or idiosyncratic adverse effects have been associated with this agent. Most frequently reported adverse effects are dizziness, ataxia, aggression, irritability, vertigo, somnolence, fatigue, headache and gait disturbance. Weight increase is the only non-neurological adverse effects associated with perampanel.
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体位于突触后膜，参与大脑中的快速兴奋性信号传递，其激活可能导致动作电位的发放。三甲噻吩烷和吡仑帕奈是首批作为附加药物在耐药性部分性癫痫发作患者中进行测试的非竞争性 AMPA 受体拮抗剂，被发现能有效改善癫痫发作的控制。由于药代动力学和耐受性不佳，三甲噻吩烷在癫痫领域的临床开发提前终止，而吡仑帕奈最近已在欧洲和美国获得批准，作为有或无继发全面性发作的成人部分性癫痫发作的辅助治疗药物。推荐的吡仑帕奈起始剂量为每天 1 次，每次 2 mg，可根据临床反应和耐受性增至推荐的维持剂量 4-8 mg/天。增量应为 2 mg/天。应根据临床反应和耐受性调整剂量。应在 1 周间隔或更慢的速度进行滴定，并且在仔细评估后应考虑每日 12 mg 的剂量。迄今为止，尚未发现与该药物相关的严重和/或特异性不良反应。最常报告的不良反应是头晕、共济失调、攻击行为、易激惹、眩晕、嗜睡、疲劳、头痛和步态障碍。体重增加是唯一与吡仑帕奈相关的非神经学不良反应。
