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The adverse effect of drugs was assessed using the chimney test. The levels of tumor necrosis factor-alpha (TNF-\u03b1) and malondialdehyde (MDA) contents were measured in mice brains after a single seizure. Administration of methadone alone resulted in a significant reduction in the duration of hind limb extension (HLE) than that in the control group. Methadone pretreatment at doses of 0.1 and 0.3 mg\/kg i.p. decreased, and at doses of 1 and 3 mg\/kg i.p. had an increasing effect on anticonvulsant efficacy of gabapentin. Pretreatment with all doses of methadone significantly decreased the valproate anticonvulsive efficacy. At doses of 1 and 3 mg\/kg i.p. methadone <jats:italic>per se<\/jats:italic> increased brain MDA levels after MES-induced seizure. Administration of methadone (0.3 mg\/kg i.p.) enhanced and at 3 mg\/kg decreased gabapentin effect on brain MDA level, but their co-treatment did not lead to further increase in MDA. Methadone at 0.3\u20133 mg\/kg enhanced the effect of sodium valproate on MDA levels in the brain, but at all doses significantly potentiated its effect on brain TNF-\u03b1 levels. The drugs did not produce any side effects on motor coordination in experimental animals. In conclusion, methadone showed different effects on anticonvulsant actions of gabapentin and valproate through regulation of brain levels of MDA and TNF-\u03b1.<\/jats:p>","DOI":"10.3389\/fneur.2022.920107","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T07:27:05Z","timestamp":1661239625000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Influence of methadone on the anticonvulsant efficacy of valproate sodium gabapentin against maximal electroshock seizure in mice by regulation of brain MDA TNF-\u03b1"],"prefix":"10.3389","volume":"13","author":[{"given":"Ali","family":"Moradi 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