Objective: In the present study, we synthesized fifteen 4, 5-disubstituted 1, 2, 4-triazol-
3-thione derivatives and evaluated for anticonvulsant activity with neurotoxicity determination.
Methods: The synthesized compounds were characterized using FTIR, 1H-NMR and MS. The
molecular docking study was also performed to study the interactions of compounds with LYS329
residue of gamma amino butyric acid aminotransferase (GABA-AT) using Autodock 4.2 software.
The anticonvulsant activity was assessed by maximal electroshock (MES) test and subcutaneous
pentylenetetrazol (scPTZ) tests. The neurotoxicity was assessed by rotarod ataxia test.
Results: In MES test, compounds 5a, 8a and 9a were found active at 100 mg/kg and five compounds
were found active at 300 mg/kg dose after 1 hr of administration. After 4 hr of drug
administration, only two compounds 8a and 9a exhibited protection at 100 mg/kg. In scPTZ test,
three compounds 2a, 6a and 8a were found active at 100 mg/kg and 7a was active at 300 mg/kg
after 1 hr of test drug administration. Most of the compounds were found active in MES test with
8a and 9a being the most active among all. In docking study, 2a was found to be best compound
based on the binding energy of -6.5 kcal/mol and estimated inhibition constant of 17.2 µM.
Conclusion: Majority of synthesized compounds were found active in MES test, whereas only
few were found to possess anti scPTZ activity. Among all compounds, only 14a caused motor coordination
impairment in rotarod ataxia test at 300 mg/kg 1 hr duration.