A new series of 6-alkoxy-[1,2,4]triazolo[3,4-a]phthalazines (3a-3v) were synthesized and their anticonvulsant activity and neurotoxicity were evaluated by the maximal electroshock test and the rotarod test respectively. Significant anticonvulsant activity was displayed by a number of compounds. The most promising compounds 6-(4-chlorobenzyloxy)-[1,2,4]triazolo[3,4-a]phthalazine (3f) and 6-heptyloxy-[1,2,4]triazolo[3,4-a]phthalazine (3s) showed a median effective dose of 7.1 and 11.0 mg/kg, and had protective index value of 5.2 and 8.0 respectively. The two compounds were further found to have potent activity against seizures induced by pentylenetetrazole, isoniazid, thiosemicarbazide, 3-mercaptopropionic acid but not seizures induced by strychnine, indicating that the two compounds might function by enhancing gamma-aminobutyric acid neurotransmission.