Background: Eplilepsy is defined as one of the most common neurological diseases,
which affects approximately 50 million people all over the word. Despite the development of several
new antiseizure drugs, the treatment of epilepsy remains still inadequate, because generally,
anticonvulsant drugs can cause serious side effects such as neurotoxicity, depression, and impaired
memory function. It is therefore imperative to search for new, safer, and more effective drugs for
Methods: All the synthesized compounds were evaluated their anticonvulsant activities by the
Maximal electroshock seizure and chemical-induced seizures models. The neurotoxicity of the
compounds was measured in mice by the rotarod test.
Results: Twenty 5-substitued-[1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-one derivatives were synthesized
and evaluated for anticonvulsant activities. Compound 5d was the most potent with an ED50
value of 27.39 mg/kg and a PI of 24.99. It also protected against seizures induced by pentylenetetrazole
and bicuculline. In addition, compound 5d exhibited an ED50 value of 76.1 mg/kg and a
PI > 39.44 following oral administration.
Conclusion: All the synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, and
Mass spectra. Compound 5-hexyl-[1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-one (5d) was safer than
the commercially available drugs carbamazepine by administration of i.p in MES test. It also protected
against seizures induced by chemical substances. Compound 5d should be a potential oral
agent for treatment of epilepsy.