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Despite the clinical impact, the mechanisms underlying the transition from self\u2010limited seizures to protracted, medically refractory seizures are not completely understood. About 40% of patients in established SE are refractory to antiepileptic drugs (first\u2010line treatment); therefore, there is a need for more efficacious drugs. In this review, we focused on the current knowledge about the involvement of alpha\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazolepropionic acid (<jats:styled-content style=\"fixed-case\">AMPA<\/jats:styled-content>) receptors during <jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content>, the preclinical efficacy of its antagonists, and the currently published clinical studies involving drugs with this mechanism of action. We carried out an extensive literature search to recognize experimental and clinical articles both on <jats:styled-content style=\"fixed-case\">AMPA<\/jats:styled-content> receptors and <jats:styled-content style=\"fixed-case\">AMPA<\/jats:styled-content> antagonists and <jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content>. Recently, the role of <jats:styled-content style=\"fixed-case\">AMPA<\/jats:styled-content> receptors during and after <jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content> has become clearer, and it is now widely accepted that early changes occur in the initial stages and probably contribute both to the maintenance of <jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content> and to its refractoriness to treatment. The therapeutic potential of <jats:styled-content style=\"fixed-case\">AMPA<\/jats:styled-content> receptor inhibition has been sustained by studies in which <jats:styled-content style=\"fixed-case\">AMPA<\/jats:styled-content> receptor antagonists have been shown to terminate seizures in several <jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content> animal models. To date, promising, but limited, data in humans support the use of <jats:styled-content style=\"fixed-case\">AMPA<\/jats:styled-content> receptor antagonists in patients with <jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">AMPA<\/jats:styled-content> receptor antagonists could become a new therapeutic option in patients with established <jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content> when the first trials with second\u2010line agents have failed or probably even better after failure of benzodiazepines as a second\u2010line option.<\/jats:p>","DOI":"10.1111\/epi.14082","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T08:16:41Z","timestamp":1523953001000},"page":"1098-1108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["The role of AMPA receptors and their antagonists in status 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