Targeting alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors in epilepsy

INTRODUCTION: Despite epilepsies being between the oldest and most studiedneurological diseases, new treatment remains an unmet need of scientific researchdue to the high percentage of refractory patients. Several studies haveidentified new suitable anti-seizure targets. Glutamate activation ofα-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) have longago been identified as suitable targets for the development of anti seizuredrugs.AREAS COVERED: Here, we describe: i) AMPARs' structure and their involvement and role during seizures and in epilepsy and ii) the efficacy of AMPAR antagonists inpreclinical models of seizures and epilepsy.EXPERT OPINION: The physiological and pathological role of AMPAR in the CNS andthe development of AMPAR antagonists have recently gained attention consideringtheir recent involvement in status epilepticus and the marketing of perampanel.The need for new anti-seizure drugs represents a major challenge in bothpreclinical and clinical epilepsy. The introduction into the market of perampanelfor the treatment of epilepsy will shed new light on the real potential of AMPAR antagonism in clinical settings outside the limited world of clinical trials.While research will go on in this area, fundamental will be the post-marketingevaluation of perampanel efficacy and tolerability and a better definition of therole of this receptor in the epileptic brain.

Introduction: Despite epilepsies being between the oldest and most studied neurological diseases, new treatment remains an unmet need of scientific research due to the high percentage of refractory patients. Several studies have identified new suitable anti-seizure targets. Glutamate activation of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) have long ago been identified as suitable targets for the development of anti seizure drugs. Areas covered: Here, we describe: i) AMPARs' structure and their involvement and role during seizures and in epilepsy and ii) the efficacy of AMPAR antagonists in preclinical models of seizures and epilepsy. Expert opinion: The physiological and pathological role of AMPAR in the CNS and the development of AMPAR antagonists have recently gained attention considering their recent involvement in status epilepticus and the marketing of perampanel. The need for new anti-seizure drugs represents a major challenge in both preclinical and clinical epilepsy. The introduction into the market of perampanel for the treatment of epilepsy will shed new light on the real potential of AMPAR antagonism in clinical settings outside the limited world of clinical trials. While research will go on in this area, fundamental will be the post-marketing evaluation of perampanel efficacy and tolerability and a better definition of the role of this receptor in the epileptic brain.