synthesis and anticonvulsant activity evaluation of 3-alkoxy-4-(4- (hexyloxy/heptyloxy)phenyl)-4h-1,2,4 -triazole

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 (ed50) of 37.3mg/kg, median toxicity dose (td50) 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 gabaa-mediated mechanisms.