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A series of 5-alkoxy-[1,2,4]triazolo[4,3-a]quinoline derivatives was synthesized using 4-hydroxyquinolin-2（1H）-one as the starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test （MES） and their neurotoxicities were measured by the rotarod test. The results of these tests demonstrated that 5-hexyloxy-[1,2,4]triazolo[4,3-a]quinoline （3f） was the most potent anticonvulsant, with median effective dose （ED50） of 19.0 mg/kg and protective index (PI = TD50/ED50) values of 5.8 in the MES test. Compound 5-benzyloxy-[1,2,4] triazolo[4,3-a]quinoline （3j）, exhibited a little weaker activity than compound 3f in controlling the seizure induced by MES test at the dose of 22.8 mg/kg, but it possessed lower neurotoxicty with PI value of 12.0, which was safer than marketed drug carbamazepine. To explain the possible mechanism of anticonvulsant activity, the compound 3j was tested in pentylenetetrazole （PTZ）, isoniazid （ISO）, thiosemi-carbazide （THIO）, 3-mercaptopropionic acid （3-MP） and strychnine （STR） test, respectively. In conclusion, compound 3j failed to protect animals from seizure induced by STR, but it produced significant antagonism activity against seizures induced by PTZ, 3-MP, THIO and ISO.
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