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Journal Article
Research Support, Non-U.S. Gov't
Synthesis and anticonvulsant activity evaluation of 4-(2-alkoxy-phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-ones in various experimental seizure models in mice.
Drug Research 2013 June
A new series of 4-(2-alkoxy-phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-ones was synthesized using appropriate synthetic route. Their anticonvulsant activities were evaluated experimentally against maximal electroshock test and their neurotoxicities were evaluated under the rotarod neurotoxicity test with intraperitoneally injected mice. The results showed that all target compounds exhibited anticonvulsant activity in varying degrees against maximal electroshock test. Among them, 4-(2-octyloxy-phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (5 g) was the most promising compound with the median effective dose (ED50) of 23.7 mg/kg, the median toxicity dose (TD50) of 611.0 mg/kg, and the protective index (PI) of 25.8. Compound 5 g showed the higher safety than the standard carbamazepine (PI=6.5). As well as demonstrating the anti-MES efficacy of compound 5 g, its potency against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline were also established, with the results suggesting that GABA-mediated mechanisms might be involved in its anticonvulsant activity.
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