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Given that the properties of the central nervous systems of these patients are likely to be altered due to their epilepsy, tissues from rodents that have undergone epileptogenesis might provide a therapeutically relevant disease substrate for identifying compounds capable of attenuating pharmacoresistant seizures. To facilitate the development of such a model, this study describes the effects of classical glutamate receptor antagonists and 20 <jats:styled-content style=\"fixed-case\">ASD<\/jats:styled-content>s on recurrent epileptiform discharges (<jats:styled-content style=\"fixed-case\">RED<\/jats:styled-content>s) in brain slices derived from the kainate\u2010induced status epilepticus model of temporal lobe epilepsy (<jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content>\u2010rats).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Horizontal brain slices containing the medial entorhinal cortex (<jats:styled-content style=\"fixed-case\">mEC<\/jats:styled-content>) were prepared from <jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content>\u2010rats, and <jats:styled-content style=\"fixed-case\">RED<\/jats:styled-content>s were recorded from the superficial layers. <jats:styled-content style=\"fixed-case\">6\u2010cyano\u20107\u2010nitroquinoxaline\u20102,3\u2010dione<\/jats:styled-content>, (2<jats:italic>R<\/jats:italic>)\u2010amino\u20105\u2010phosphonovaleric acid, <jats:styled-content style=\"fixed-case\">tetrodotoxin<\/jats:styled-content>, or <jats:styled-content style=\"fixed-case\">ASD<\/jats:styled-content>s were bath applied for 20\u00a0minutes. Concentration\u2010dependent effects and half maximal effective concentration values were determined for <jats:styled-content style=\"fixed-case\">RED<\/jats:styled-content> duration, frequency, and amplitude.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ASDs targeting sodium and potassium channels (carbamazepine, eslicarbazepine, ezogabine, lamotrigine, lacosamide, phenytoin, and rufinamide) attenuated <jats:styled-content style=\"fixed-case\">RED<\/jats:styled-content>s at concentrations near their average therapeutic plasma concentrations. \u03b3\u2010aminobutyric acid (<jats:styled-content style=\"fixed-case\">GABA)<\/jats:styled-content>ergic synaptic transmission\u2013modulating <jats:styled-content style=\"fixed-case\">ASD<\/jats:styled-content>s (clobazam, midazolam, phenobarbital, stiripentol, tiagabine, and vigabatrin) attenuated <jats:styled-content style=\"fixed-case\">RED<\/jats:styled-content>s only at higher concentrations and, in some cases, prolonged <jats:styled-content style=\"fixed-case\">RED<\/jats:styled-content> durations. <jats:styled-content style=\"fixed-case\">ASD<\/jats:styled-content>s with other\/mixed mechanisms of action (bumetanide, ethosuximide, felbamate, gabapentin, levetiracetam, topiramate, and valproate) and glutamate receptor antagonists weakly or incompletely inhibited <jats:styled-content style=\"fixed-case\">RED<\/jats:styled-content> frequency, increased <jats:styled-content style=\"fixed-case\">RED<\/jats:styled-content> duration, or had no significant effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Taken together, these data suggest that epileptiform activity recorded from the superficial layers of the <jats:styled-content style=\"fixed-case\">mEC<\/jats:styled-content> in slices obtained from <jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content>\u2010rats is differentially sensitive to existing <jats:styled-content style=\"fixed-case\">ASD<\/jats:styled-content>s. The different sensitivities of <jats:styled-content style=\"fixed-case\">RED<\/jats:styled-content>s to these <jats:styled-content style=\"fixed-case\">ASD<\/jats:styled-content>s may reflect persistent molecular, cellular, and\/or network\u2010level changes resulting from disease. These data are expected to serve as a foundation upon which future therapeutics may be differentiated and assessed for potentially translatable efficacy in patients with refractory epilepsy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.14563","type":"journal-article","created":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T09:23:04Z","timestamp":1539768184000},"page":"2035-2048","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Recurrent epileptiform discharges in the medial entorhinal cortex of kainate\u2010treated rats are differentially sensitive to antiseizure drugs"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5774-5180","authenticated-orcid":false,"given":"Peter J.","family":"West","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Utah Salt Lake City Utah"},{"name":"Epilepsy Therapy Screening Program (ETSP) Contract Site University of Utah Salt Lake City Utah"},{"name":"Interdepartmental Neuroscience Program University of Utah Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald W.","family":"Saunders","sequence":"additional","affiliation":[{"name":"Epilepsy Therapy Screening Program (ETSP) Contract Site University of Utah Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Billingsley","sequence":"additional","affiliation":[{"name":"Epilepsy Therapy Screening Program (ETSP) Contract Site University of Utah Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misty D.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Utah Salt Lake City Utah"},{"name":"Epilepsy Therapy Screening Program (ETSP) Contract Site University of Utah Salt Lake City Utah"},{"name":"School of Dentistry University of Utah Salt Lake City Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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