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In this study, the impact of lacosamide and perampanel alone and in combination was tested in corneal kindling model in mice, which is a cost\u2010effective mechanism for screening of antiseizure drugs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The impact of lacosamide (5\u2009mg\/kg) and perampanel (0.125\u2009mg\/kg) alone and their combination was tested in corneal kindling process (3\u2010mA current for 3\u2009s applied twice daily for consecutive 12\u2009days) in male BALB\/c mice. Post\u2010kindling, mice were subjected to a battery of behavioral tests assessing anxiety, memory, and depression\u2010like behaviors. Brain tissues were then harvested for analysis of oxidative stress biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results showed that the combination therapy of lacosamide and perampanel was more effective in reducing seizure progression than monotherapy of these drugs. Animals treated with combination therapy showed significant behavioral improvements, as reduced anxiety and depression were noticed, and their cognitive abilities were notably better compared to animals of all other groups. Moreover, biochemical assays of isolated brains from combination\u2010treated group revealed lesser amount of oxidative stress. In addition, outcomes of dual regime were comparable to the phenytoin in seizure control but showed superior benefits in mitigation of kindling\u2010prompted behavioral dysfunction and oxidative stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study suggests that the lacosamide and perampanel combination therapy worked noticeably better in halting the corneal kindling process in mice and improved the epilepsy\u2010associated psychiatric disorders that might be due to antioxidant effects of both drugs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12524","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T12:14:31Z","timestamp":1737634471000},"page":"222-238","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Unraveling the neuroprotective effect of perampanel and lacosamide combination in the corneal kindling model for epilepsy in 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