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The interaction profile of four classic antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) with TPL-16 was also determined in the tonic-clonic seizure model in mice. The protective effects of TPL-16 from tonic-clonic seizures (as ED<jats:sub>50<\/jats:sub> values) and acute neurotoxic effects of TPL-16 (as TD<jats:sub>50<\/jats:sub> values) were determined in 4 pretreatment times (15, 30, 60 and 120\u00a0min after its i.p. administration), in adult male albino Swiss mice. The interaction profile of TPL-16 with carbamazepine, phenobarbital, phenytoin and valproate in the tonic-clonic seizure model was determined with isobolographic analysis. Total concentrations of carbamazepine, phenobarbital, phenytoin and valproate were measured in the mouse brain homogenates. The candidate for novel antiepileptic drug (TPL-16) administered separately 15\u00a0min before experiments, has a beneficial profile with protective index (as ratio of TD<jats:sub>50<\/jats:sub> and ED<jats:sub>50<\/jats:sub> values) amounting to 5.58. The combination of TPL-16 with valproate produced synergistic interaction in the tonic-clonic seizure model in mice. The combinations of TPL-16 with carbamazepine, phenobarbital and phenytoin produced additive interaction in terms of protection from tonic-clonic seizures in mice. None of the total brain concentrations of classic AEDs were changed significantly after TPL-16 administration in mice. Synergistic interaction for TPL-16 with valproate and the additive interaction for TPL-16 with carbamazepine, phenobarbital and phenytoin in the tonic-clonic seizures in mice allows for recommending TPL-16 as the promising drug for further experimental and clinical testing.<\/jats:p>","DOI":"10.1007\/s11064-020-03175-z","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T16:04:07Z","timestamp":1605715447000},"page":"396-410","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Anticonvulsant Effectiveness and Neurotoxicity Profile of 4-butyl-5-[(4-chloro-2-methylphenoxy)methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (TPL-16) in Mice"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4424-4915","authenticated-orcid":false,"given":"Magdalena","family":"Drabik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"G\u0142uszak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7099-1968","authenticated-orcid":false,"given":"Paula","family":"Wr\u00f3blewska-\u0141uczka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6255-5085","authenticated-orcid":false,"given":"Zbigniew","family":"Plewa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9900-9168","authenticated-orcid":false,"given":"Marek","family":"Jankiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8817-5638","authenticated-orcid":false,"given":"Justyna","family":"Kozi\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1489-2399","authenticated-orcid":false,"given":"Magdalena","family":"Florek-\u0141uszczki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8162-8435","authenticated-orcid":false,"given":"Tomasz","family":"Plech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3059-0393","authenticated-orcid":false,"given":"Jarogniew J.","family":"\u0141uszczki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,18]]},"reference":[{"key":"3175_CR1","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1212\/WNL.0000000000003509","volume":"88","author":"KM Fiest","year":"2017","unstructured":"Fiest KM, Sauro KM, Wiebe S et al (2017) Prevalence and incidence of epilepsy. 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