Synthesis and neuropharmacological activity of some quinoxalinone derivatives

Olayiwola, G. ; Obafemi, C.A. ; Taiwo, F.O (3/19/2007)



Eight quinoxalinone derivatives were synthesized and investigated for some neuropharmacological effects (analgesia, sedation, convulsion, anxiety, memory and psychosis) in mice and rats. In the CNS depressant activity, N,N-dibenzyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide is the most active, while the other compounds appear variously dose-dependent. Only three of the compounds showed anxiolytic effect, with N,N-dibenzyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide showing the highest activity at 2.5 mg/kg. At the dose of 30 mg/kg, 6-nitro-1,4-dihydroquinoxaline-2,3-dione showed a better anxiolytic effect in mice than diazepam (dose: 1 mg/kg), while 1,2,3,4-tetrahydroquinoxaline-2,3-dione (dose: 25 mg/kg) showed a comparative effect to diazepam. 6-Chloro-1,4-dihydro-quinoxaline-2,3-dione and N,N-dibenzyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide showed significant anticonvulsant action. None of the compounds showed any analgesic or antidopaminergic effect. The LD50 (24 h) calculated for the compounds were between 74 and 160 mg/kg i.p.