{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:51:50Z","timestamp":1791276710042,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007132","name":"Otsuka Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropsychopharm Rep"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Dravet syndrome (DS) is a severe and treatment\u2010resistant epileptic encephalopathy, most commonly caused by de novo mutations in the sodium voltage\u2010gated channel alpha subunit 1 (\n                      <jats:italic>SCN1A<\/jats:italic>\n                      ) gene. Patients with DS often present with febrile seizures. It has been reported that\n                      <jats:italic>Scn1a<\/jats:italic>\n                      mutant mice have the risk for hyperthermia\u2010induced clonic seizures similar to those observed in patients with DS. Using our heating protocol with an incubator, we evaluated the effects of antiseizure medications on the incidence of hyperthermia\u2010induced clonic seizures in mutant\n                      <jats:italic>Scn1a<\/jats:italic>\n                      knock\u2010in (KI)\/+ mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      For clonic seizure induction in\n                      <jats:italic>Scn1a<\/jats:italic>\n                      KI\/+ mice, each mouse was placed into an incubator (38\u00b0C\u201340\u00b0C) and observed for 15\u2009min. Antiseizure medications were administered orally 30\u2009min prior to the experiment. The time to seizure onset and the incidence of clonic seizures were analyzed to evaluate and compare the antiseizure effects among treatment groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our incubation system increased the body temperature of mice and induced clonic seizures in\n                      <jats:italic>Scn1a<\/jats:italic>\n                      KI\/+ mice. Clobazam (CLB) and valproate (VPA) significantly reduced the incidence of hyperthermia\u2010induced clonic seizures in\n                      <jats:italic>Scn1a<\/jats:italic>\n                      KI\/+ mice, with 50% effective dose (ED\n                      <jats:sub>50<\/jats:sub>\n                      ) values of 1.94\u2009mg\/kg (95% confidence interval [CI]: 0.93\u20133.89\u2009mg\/kg) and 255.87\u2009mg\/kg (95% CI: 188.66\u2013356.85\u2009mg\/kg) respectively, and prolonged the time to seizure onset. In contrast, lamotrigine (LTG), a sodium channel blocker, did not reduce the incidence of hyperthermia\u2010induced seizures. CLB and LTG did not affect the body temperature. VPA decreased the body temperature compared to the vehicle\u2010treated mice before and after incubation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These results reflect clinical findings that CLB and VPA suppress, but LTG does not suppress seizures in patients with DS. Our data demonstrate the validity of our test system to induce hyperthermia\u2010induced seizures and to evaluate the efficacy of antiseizure medications in\n                      <jats:italic>Scn1a<\/jats:italic>\n                      KI\/+ mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/npr2.70168","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:46:21Z","timestamp":1789519581000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clobazam and Valproate, but Lamotrigine, a Sodium Channel Inhibitor, Reduce the Incidence of Hyperthermia\u2010Induced Clonic Seizures in Dravet Syndrome Mice: Assessment of Anti\u2010Seizure Effects in Mice Using a Stabilized Ambient Temperature System"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7664-4527","authenticated-orcid":false,"given":"Futa","family":"Sato","sequence":"first","affiliation":[{"name":"Department of CNS Research Otsuka Pharmaceutical Co. Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayuka","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of CNS Research Otsuka Pharmaceutical Co. Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3403-7145","authenticated-orcid":false,"given":"Megumi","family":"Oishi","sequence":"additional","affiliation":[{"name":"Department of CNS Research Otsuka Pharmaceutical Co. Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6856-2515","authenticated-orcid":false,"given":"Yuki","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of CNS Research Otsuka Pharmaceutical Co. Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9625-6240","authenticated-orcid":false,"given":"Naoki","family":"Amada","sequence":"additional","affiliation":[{"name":"Department of CNS Research Otsuka Pharmaceutical Co. Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5600-5538","authenticated-orcid":false,"given":"Takashi","family":"Wadatsu","sequence":"additional","affiliation":[{"name":"Department of Lead Discovery Research Otsuka Pharmaceutical Co. Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9072-1342","authenticated-orcid":false,"given":"Nobuyoshi","family":"Jinnai","sequence":"additional","affiliation":[{"name":"Department of Lead Discovery Research Otsuka Pharmaceutical Co. Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2686-8593","authenticated-orcid":false,"given":"Yusuke","family":"Kakumoto","sequence":"additional","affiliation":[{"name":"Department of Lead Discovery Research Otsuka Pharmaceutical Co. Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Maeda","sequence":"additional","affiliation":[{"name":"Medical Affairs Department Otsuka Pharmaceutical Co. Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7904-342X","authenticated-orcid":false,"given":"Yuki","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Lead Discovery Research Otsuka Pharmaceutical Co. Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Futamura","sequence":"additional","affiliation":[{"name":"Department of CNS Research Otsuka Pharmaceutical Co. Ltd.  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