RESUMO
A series of 3-alkoxy-4-[4-[hexyloxy/heptyloxy] phenyl]-4H-1,2,4-triazole was synthesized. The anticonvulsant effect and neurotoxicity of the compounds were calculated with maximal electroshock [MES] test and rotarod tests with intraperitoneally injected mice. Among the synthesized compounds, compound 3-heptyloxy-4-[4-[hexyloxy] phenyl]-4H-1,2,4-triazole [5f] was the most active one and also had the lowest toxicity. In the anti-MES potency test, it showed median effective dose [ED[50]] of 37.3 mg/Kg, median toxicity dose [TD[50]] of 422.5 mg/Kg, and the protective index [PI] of 11.3 which is much greater than the reference drug carbamazepine with PI value of 6.4. As well as demonstrating the anti-MES efficacy of compound 5f, 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, such as enhancing of GABAergic neurotransmission or activity, activate GAD or inhibit GABA-T, and GABA[A]-mediated mechanisms