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This model of pharmacoresistant epilepsy has been incorporated into the testing scheme utilized by the Epilepsy Therapy Screening Program (ETSP). Although some ASDs have been evaluated in this model, a comprehensive evaluation of ASD prototypes has not been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Following depth electrode implantation and recovery, rats were exposed to lamotrigine (5\u00a0mg\/kg, i.p.) prior to each stimulation during the kindling development process (~3\u00a0weeks). A test dose of lamotrigine was used to confirm that fully kindled rats were lamotrigine\u2010resistant. Efficacy (unambiguous protection against electrically elicited convulsive seizures) was defined as a Racine score\u00a0&lt;\u00a03 in the absence of overt compound\u2010induced side effects. Various ASDs, comprising several mechanistic classes, were administered to fully kindled, lamotrigine\u2010resistant rats. Where possible, multiple doses of each drug were administered in order to obtain median effective dose (ED<jats:sub>50<\/jats:sub>) values.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five sodium channel blockers tested (eslicarbazepine, lacosamide, lamotrigine, phenytoin, and rufinamide) were either not efficacious or effective only at doses that were not well\u2010tolerated in this model. In contrast, compounds targeting either GABA receptors (clobazam, clonazepam, phenobarbital) or GABA\u2010uptake proteins (tiagabine) produced dose\u2010dependent efficacy against convulsive seizures. Compounds acting to modulate Ca<jats:sup>2+<\/jats:sup> channels show differential activity: Ethosuximide was not effective, whereas gabapentin was moderately efficacious. Ezogabine and valproate were also highly effective, whereas topiramate and levetiracetam were not effective at the doses tested.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>These results strengthen the conclusion that the lamotrigine\u2010resistant amygdala kindling model demonstrates pharmacoresistance to certain ASDs, including, but not limited to, sodium channel blockers, and supports the utility of the model for helping to identify compounds with potential efficacy against pharmacoresistant seizures.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12354","type":"journal-article","created":{"date-parts":[[2019,8,2]],"date-time":"2019-08-02T10:34:57Z","timestamp":1564742097000},"page":"452-463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Evaluation of antiseizure drug efficacy and tolerability in the rat lamotrigine\u2010resistant amygdala kindling model"],"prefix":"10.1002","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1510-0405","authenticated-orcid":false,"given":"Cameron S.","family":"Metcalf","sequence":"first","affiliation":[{"name":"Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Huff","sequence":"additional","affiliation":[{"name":"Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle E.","family":"Thomson","sequence":"additional","affiliation":[{"name":"Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Johnson","sequence":"additional","affiliation":[{"name":"Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon F.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen S.","family":"Wilcox","sequence":"additional","affiliation":[{"name":"Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2016.05.016"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1499-1654.2000.001514.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7343"},{"key":"e_1_2_8_5_1","first-page":"483","article-title":"Kindling as a model of drug\u2010resistant partial epilepsy: selection of phenytoin\u2010resistant and nonresistant rats","volume":"258","author":"Loscher W","year":"1991","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2014.05.008"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.00980.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1998.tb01289.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(98)00087-4"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(00)00108-X"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2012.10.003"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12234"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2275-z"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2222-z"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2015.11.007"},{"key":"e_1_2_8_16_1","unstructured":"2014 NINDS Benchmarks for Epilepsy Research 2018. 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