A series of 5-substituted-[1,2,4]triazolo[4,3-a]quinazolines were synthesized. The anticonvulsant effects and neurotoxicity of the compounds were evaluated with maximal electroshock test and rotarod test with intraperitoneally injected in mice. The pharmacology results showed that 5-pentyloxy-[1,2,4]triazolo- [4,3-a]quinazoline (2d) was the most potent with ED₅₀ value of 19.7 mg/kg and protective index (PI＝TD₅₀/ED₅₀) value of 6.2. To explain the possible mechanism of anticonvulsant activity, compound 2d was tested in several chemical induced seizures tests. The results revealed that compound 2d was effective against the seizures induced by pentylenetetrazole, isoniazid, 3-mercaptopropionic acid and thiosemicarbazide, which suggested that the anticonvulsant effects of this series compounds were acted via increasing γ-aminobutyric acid (GABA) ergic neurotransmission and activating glutamate decarboxylase (GAD) or inhibiting α-oxoglutarate aminotransferase (GABA-T) in the brain.

Key words: triazoloquinazoline, synthesis, anticonvulsant, pentylenetetrazole, rotarod test