Di Bonaventura Carlo, Labate Angelo, Maschio Marta, Meletti Stefano, Russo Emilio
a Department of Neurology and Psychiatry, Neurology Unit , 'Sapienza' University , Rome , Italy.
b Institute of Neurology , University Magna Graecia of Catanzaro , Catanzaro , Italy.
Expert Opin Pharmacother. 2017 Nov;18(16):1751-1764. doi: 10.1080/14656566.2017.1392509. Epub 2017 Oct 17.
The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are the major mediators of glutamate-mediated excitatory neurotransmission, and are critical for synchronization and spread of epileptic activity. Areas covered: AMPA receptor antagonists have been also developed as antiepileptic drugs and perampanel (PER) is the first highly selective, non-competitive AMPA-type glutamate receptor antagonist that is available on the market. It is approved as adjunctive therapy for the treatment of partial-onset seizures with or without secondary generalization, and for primary generalized tonic-clonic seizures in idiopathic generalized epilepsy, in patients aged ≥ 12 years. This article reviews the role of AMPA receptors in the neuronal hyperexcitability underlying epilepsy, the mechanism of action and clinical experience on the anti-seizure activity of PER. Moreover, the rationale for targeting AMPA receptor in specific epileptic disorders, including brain tumor-related epilepsy, mesial temporal lobe epilepsy with/without hippocampal sclerosis, and status epilepticus is evaluated. Finally, the pharmacological rationale for the development of AMPA receptor antagonists in other neurological disorders beyond epilepsy is considered. Expert opinion: Further research aimed at better understanding the pharmacology and blocking mechanism of PER and other AMPA receptor antagonists will drive future development of therapeutic agents that target epilepsy and other neurological diseases.
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体是谷氨酸介导的兴奋性神经传递的主要介质，对癫痫活动的同步化和扩散至关重要。涵盖领域：AMPA受体拮抗剂也已被开发为抗癫痫药物，吡仑帕奈（PER）是市场上首个高度选择性、非竞争性的AMPA型谷氨酸受体拮抗剂。它被批准作为辅助疗法，用于治疗≥12岁患者的伴有或不伴有继发性全面发作的部分性发作，以及特发性全身性癫痫中的原发性全身性强直阵挛发作。本文综述了AMPA受体在癫痫相关神经元兴奋性过高中的作用、PER抗癫痫活性的作用机制和临床经验。此外，还评估了在特定癫痫疾病中靶向AMPA受体的理论依据，包括脑肿瘤相关性癫痫、伴或不伴海马硬化的内侧颞叶癫痫以及癫痫持续状态。最后，探讨了在癫痫以外的其他神经系统疾病中开发AMPA受体拮抗剂的药理学依据。专家观点：旨在更好地理解PER和其他AMPA受体拮抗剂的药理学及阻断机制的进一步研究，将推动针对癫痫和其他神经系统疾病的治疗药物的未来发展。
