{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T16:10:24Z","timestamp":1782490224003,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,4,27]],"date-time":"2017-04-27T00:00:00Z","timestamp":1493251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["HHSN271201100029C"],"award-info":[{"award-number":["HHSN271201100029C"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The mouse 6 Hz model of psychomotor seizures is a well\u2010established and commonly used preclinical model for antiseizure drug (ASD) discovery. Despite its widespread use both in the identification and differentiation of novel ASDs in mice, a corresponding assay in rats has not been developed. We established a method for 6 Hz seizure induction in rats, with seizure behaviors similar to those observed in mice including head nod, jaw clonus, and forelimb clonus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A convulsive current that elicits these seizure behaviors in 97% of rats (CC<jats:sub>97<\/jats:sub>) was determined using a Probit analysis. Numerous prototype ASDs were evaluated in this model using stimulus intensities of 1.5\u00d7 and 2\u00d7 the CC<jats:sub>97<\/jats:sub>, which is comparable to the approach used in the mouse 6 Hz seizure model (e.g., 32 and 44 mA stimulus intensities). The ASDs evaluated include carbamazepine, clobazam, clonazepam, eslicarbazepine, ethosuximide, ezogabine, gabapentin, lacosamide, lamotrigine, levetiracetam, phenobarbital, phenytoin, rufinamide, tiagabine, topiramate, and sodium valproate. Median effective dose (ED<jats:sub>50<\/jats:sub>) and median toxic (motor impairment) dose (TD<jats:sub>50<\/jats:sub>) values were obtained for each compound.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compounds that were effective at the 1.5 \u00d7 CC<jats:sub>97<\/jats:sub>stimulus intensity at protective index (PI) values &gt;1 included clobazam, ethosuximide, ezogabine, levetiracetam, phenobarbital, and sodium valproate. Compounds that were effective at the 2 \u00d7 CC<jats:sub>97<\/jats:sub>stimulus intensity at PI values &gt;1 included ezogabine, phenobarbital, and sodium valproate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>In a manner similar to the use of the mouse 6 Hz model, development of a rat 6 Hz test will aid in the differentiation of ASDs, as well as in study design and dose selection for chronic rat models of pharmacoresistant epilepsy. The limited number of established ASDs with demonstrable efficacy at the higher stimulus intensity suggests that, like the mouse 6 Hz 44 mA model, the rat 6 Hz seizure model may be a useful screening tool for pharmacoresistant seizures.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13764","type":"journal-article","created":{"date-parts":[[2017,4,27]],"date-time":"2017-04-27T21:38:39Z","timestamp":1493329119000},"page":"1073-1084","source":"Crossref","is-referenced-by-count":79,"title":["Development and pharmacologic characterization of the rat 6 Hz model of partial seizures"],"prefix":"10.1111","volume":"58","author":[{"given":"Cameron S.","family":"Metcalf","sequence":"first","affiliation":[{"name":"Anticonvulsant Drug Development Program Department of Pharmacology and Toxicology University of Utah Salt Lake City Utah U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5774-5180","authenticated-orcid":false,"given":"Peter J.","family":"West","sequence":"additional","affiliation":[{"name":"Anticonvulsant Drug Development Program Department of Pharmacology and Toxicology University of Utah Salt Lake City Utah U.S.A."}],"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 Utah U.S.A."}],"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 Utah U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misty D.","family":"Smith","sequence":"additional","affiliation":[{"name":"Anticonvulsant Drug Development Program Department of Pharmacology and Toxicology University of Utah Salt Lake City Utah U.S.A."},{"name":"School of Dentistry University of Utah Salt Lake City Utah U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Steve","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Washington Seattle Washington U.S.A."}],"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 Utah U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.1.11-12.444"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0022-3565(25)05160-2","article-title":"Comparative assay of an antiepileptic drugs by psychomotor seizure test and minimal electroshock threshold test","volume":"107","author":"Brown WC","year":"1953","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(01)00302-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2003.08.001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2012.10.001"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2015.01.001"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2009.06.003"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm801088x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2009.01.001"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2006.10.008"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2008.09.005"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2010.09.001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03364.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-015-1360-6"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12296"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2997"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2011.01.003"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12234"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2012.10.003"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2015.03.025"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms140918284"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0980-08.2009"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-016-2025-7"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/acprof:oso\/9780195178081.001.0001"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1017\/CHOL9780521077910"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141221"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2016.05.016"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12893"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.13764","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.13764","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:52:21Z","timestamp":1750207941000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.13764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,27]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1111\/epi.13764"],"URL":"https:\/\/doi.org\/10.1111\/epi.13764","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,27]]}}}