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Rep"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Overwhelming evidence indicates that some naturally occurring coumarins and terpenes are widely used in folk medicine due to their various therapeutic effects affecting the brain. Antiseizure medications (ASMs) are the principal treatment option for epilepsy patients, although some novel strategies based on naturally occurring substances are intensively investigated. This study was aimed at determining the influence of isopimpinellin (ISOP\u2014a coumarin) when administered either separately or in combination with borneol (BOR\u2014a monoterpenoid), on the antiseizure potencies of four classic ASMs (carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), and valproate (VPA)) in the mouse model of maximal electroshock-induced (MES) tonic\u2013clonic seizures.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Materials<\/jats:title>\n                <jats:p>Tonic\u2013clonic seizures were evoked experimentally in mice after systemic (<jats:italic>ip<\/jats:italic>) administration of the respective doses of ISOP, BOR, and classic ASMs. Interactions for two-drug (ISOP\u2009+\u2009a classic ASM) and three-drug (ISOP\u2009+\u2009BOR\u2009+\u2009a classic ASM) mixtures were assessed isobolographically in the mouse MES model.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>ISOP (administered alone) had no impact on the anticonvulsant potencies of four classic ASMs. Due to the isobolographic transformation of data, the combination of ISOP\u2009+\u2009VPA exerted an antagonistic interaction, whereas the two-drug mixtures of ISOP\u2009+\u2009CBZ, ISOP\u2009+\u2009PHT, and ISOP\u2009+\u2009PB produced additive interactions in the mouse MES model. The three-drug combinations of ISOP\u2009+\u2009BOR with CBZ and PHT produced additive interactions, while the three-drug combinations of ISOP\u2009+\u2009BOR with PB and VPA exerted synergistic interactions in the mouse MES model.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The most intriguing interaction was that for ISOP\u2009+\u2009VPA, for which the addition of BOR evoked a transition from antagonism to synergy in the mouse MES model.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s43440-023-00532-x","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:13:41Z","timestamp":1697055221000},"page":"1533-1543","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Anticonvulsant effects of isopimpinellin and its interactions with classic antiseizure medications and borneol in the mouse tonic\u2013clonic seizure model: an isobolographic transformation"],"prefix":"10.1007","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3059-0393","authenticated-orcid":false,"given":"Jarogniew J.","family":"\u0141uszczki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4887-7541","authenticated-orcid":false,"given":"Hubert","family":"Bojar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5453-4460","authenticated-orcid":false,"given":"Katarzyna","family":"Jankiewicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1489-2399","authenticated-orcid":false,"given":"Magdalena","family":"Florek-\u0141uszczki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2606-1656","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Chmielewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9313-5929","authenticated-orcid":false,"given":"Krystyna","family":"Skalicka-Wo\u017aniak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"532_CR1","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/S0140-6736(18)32596-0","volume":"393","author":"RD Thijs","year":"2019","unstructured":"Thijs RD, Surges R, O\u2019Brien TJ, Sander JW. 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