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In this study, a series of new 5-alkoxy-[1,2,4]triazolo[4,3-a]pyridine derivatives was synthesized and their anticonvulsant activity and neurotoxicity was evaluated with the maximal electroshock and rotarod tests, respectively. The most promising compounds, 3p (5-(4-chlorophenoxy)-[1,2,4]triazolo[4,3-a]pyridine) and 3r (5-(4-bromophenoxy)-[1,2,4]triazolo[4,3-a]pyridine), showed a median effective dose of 13.2 and 15.8 mg/kg and had a protective index value of 4.8 and 6.9, respectively. For exploring the putative mechanism of action, compounds 3n, 3p and 3r were tested in chemically induced models.
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