Synthesis And Anticonvulsant Activities Of2,9-Dihydro-3H-[1,2,4]-Triazolo[4,3-a]Benzimidazole-3-Ones

A series novel of benzimidazole derivatives were synthesized, then screene d by MES and TOX for their anticonvulsant activities and neurotoxicities. Anti convulsant activities and neurotoxicities of compounds when injected intraperito neally were determined by maximal electroshock seizure (MES) test and a rota rod neurotoxicity test (Tox),9-(2,6-dichlorobenzyl)-2,9-dihydro-3H-[1,2,4]-triazolo [4,3-a]benzimidazole-3-one4p was a remarkable compound which has more act ive and lower toxicity among all synthesized compounds. In these test,4p exhi bited median effective dose (ED50) values of31.69mg/kg, a median toxicity d ose (TD50) values beyond350mg/kg, and the protective index (PI=TD50/ED50) values of>11.04by intraperitoneal administration in the MES. And compou nd4p exhibited ED50values of44.01mg/kg and the PI values of31.6by ora1administration. To further investigate the effects of the anticonvulsant activity in several different models. Compound4p was tested against convulsions indu ced by chemical substances, including pentylenetetrazole,3-mercamtopropionic a cid and bicuculline to research the anticonvulsant mechanism of compound4p. It is believed that compound4p is the lead compound as a new antiepilepsy drug in the future research.