Tricyclic heteroaromatic systems. 3-substituted 1,2,3,5,6,7-hexahydro-2,5,6-trioxopyrazino[1,2,3-de]-quinoxalines as novel antagonists at the glycine-NMDA site.

Two novel antagonists of the glycine-NMDA receptor have been synthesized and tested for their ability to displace [ 3 H]glycine from the specific binding site in rat brain cortical membranes. The 3-substituted pyrazino[1,2,3-de]quinoxaline-2,5,6-triones 1a-b contain all the essential pharmacophoric descriptors of a glycine receptor antagonist. A model is proposed for the binding of these compounds that includes some of the interactions postulated for the potent glycine-NMDA receptor antagonist L-689560