A series of 4,5-dihydro-1,2,4-triazolo[1,5-a]quinoxalin-4-ones bearing different substituents on the benzo-fused ring and at position 2 were synthesized and biologically evaluated for their binding at glycine/NMDA and AMPA receptors. Most of the reported compounds show combined glycine/NMDA and AMPA receptor binding activity providing further evidences of the structural similarities of the binding pockets of both receptor recognition sites. Moreover, this study has pointed out some differences for the binding at each receptor type. In particular, for the glycine/NMDA receptor-ligand interaction, the presence of a free acidic function at position 2 and an electron-withdrawing substituent(s) nonbulkier than chlorine atom(s) on the benzo-fused moiety is required. Functional antagonism at the NMDA receptor-ion channel complex was also performed on some selected compounds.