{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T17:42:08Z","timestamp":1781199728201,"version":"3.54.1"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      T\u2010type Ca\n                      <jats:sup>2+<\/jats:sup>\n                      channels in the brain contribute to the generation of spike\u2010and\u2010wave discharges (SWDs). Absence seizures are defined by the occurrence of SWDs and are associated with impairment of consciousness. ACT\u2010709478 is a selective and highly potent blocker of the low\u2010voltage\u2010activated T\u2010type Ca\n                      <jats:sup>2+<\/jats:sup>\n                      channels, Ca\n                      <jats:sub>v<\/jats:sub>\n                      3.1, Ca\n                      <jats:sub>v<\/jats:sub>\n                      3.2, and Ca\n                      <jats:sub>v<\/jats:sub>\n                      3.3, with no relevant activity on other targets. Our aim was to investigate the efficacy of ACT\u2010709478 in reducing absence\u2010like and other types of seizures in rodents.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We studied the effect of oral ACT\u2010709478 on SWDs in two models of absence\u2010like epilepsy, Wistar Albino Glaxo from Rijswijk (WAG\/Rij) rats and Genetic Absence Epilepsy Rats from Strasbourg (GAERS), and compared it to first\u2010line monotherapy. We also assessed the potential of ACT\u2010709478 to reduce generalized convulsive seizures in audiogenic seizure\u2010sensitive (AGS) mice and in the maximal electroshock threshold test (MEST) in mice, as well as in one model of focal onset seizures, the amygdala kindling rat model. We tested combinations of ACT\u2010709478 with the broadly used first\u2010line medication valproate in AGS mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ACT\u2010709478 suppressed SWDs in WAG\/Rij rats and GAERS with efficacy equivalent to or superior to that of first\u2010line monotherapy. ACT\u2010709478 also reduced the severity of generalized convulsive seizures in the AGS mouse model and the MEST in mice, albeit at higher concentration. ACT\u2010709478 had synergistic effects against generalized convulsive seizures, when combined with valproate, and had no effect on focal onset seizures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Based on its efficacy profile in rodent models, ACT\u2010709478 represents a promising drug candidate for the treatment of absence epilepsy such as childhood absence epilepsy or syndromes featuring SWDs. It could possibly also be beneficial for epileptic syndromes presenting with additional seizure types.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18386","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:05Z","timestamp":1743552005000},"page":"2554-2565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antiseizure potential of the triple T\u2010type calcium channel blocker\n                    <scp>ACT<\/scp>\n                    \u2010709478 (apinocaltamide) in rodent models"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3577-7869","authenticated-orcid":false,"given":"Melanie","family":"Kessler","sequence":"first","affiliation":[{"name":"Department of Drug Discovery, CNS\u2010Pharmacology Division Idorsia Pharmaceuticals  Allschwil 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