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This study evaluated the effect of XANT on the ability of classical and novel antiepileptic drugs to prevent seizures evoked by the 6\u2010Hz corneal stimulation\u2010induced seizure model, which is thought to be an experimental model of psychomotor (limbic) seizures in humans. XANT (50\u2009mg\/kg, administered i.p.) significantly potentiated the anticonvulsant activity of levetiracetam and valproate, decreasing their median effective dose (ED<jats:sub>50<\/jats:sub>) values from 19.37 to 2.83\u2009mg\/kg (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01) for levetiracetam and from 92.89 to 44.44\u2009mg\/kg (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) for valproate. Neither XANT (50\u2009mg\/kg) alone nor its combination with the anticonvulsant drugs (at their ED<jats:sub>50<\/jats:sub> values from the 6\u2010Hz test) affected motor coordination; skeletal muscular strength and long\u2010term memory, as determined in the chimney; and grip strength and passive avoidance tests, respectively. Measurement of total brain antiepileptic drug concentrations revealed that XANT (50\u2009mg\/kg) had no impact on levetiracetam total brain concentrations, indicating the pharmacodynamic nature of interaction between these antiepileptic drugs in the mouse 6\u2010Hz model. However, XANT (50\u2009mg\/kg, i.p.) significantly increased total brain concentrations of valproate (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), indicating the pharmacokinetic nature of interactions between drugs. XANT in combination with levetiracetam exerts beneficial anticonvulsant pharmacodynamic interactions in the 6\u2010Hz mouse psychomotor seizure model.<\/jats:p>","DOI":"10.1111\/fcp.12713","type":"journal-article","created":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T00:31:30Z","timestamp":1625272290000},"page":"133-142","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Xanthotoxin enhances the anticonvulsant potency of levetiracetam and valproate in the 6\u2010Hz corneal stimulation model in mice"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0079-0490","authenticated-orcid":false,"given":"Miros\u0142aw","family":"Zagaja","sequence":"first","affiliation":[{"name":"Isobolographic Analysis Laboratory Institute of Rural Health  Lublin 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