Quinoxalinediones selectively block quisqualate and kainate receptors and synaptic events in rat neocortex and hippocampus and frog spinal cord in vitro

Pharmacological characterization of non‐NMDA subtypes of glutamate receptor in the neonatal rat hemisected spinal cord in vitro

“…Depolarizations evoked by agonist superfusion of the hemisected cord were reproducible and of similar amplitude to those seen in the cortical wedge preparation (Harrison & Simmonds, 1985;Fletcher et al, 1988). As with the cortical wedge, NMDA, AMPA and kainate were approximately equipotent and high doses of each agonist led to irreversible reductions in amplitude of all subsequent agonist responses, which is presumably a reflection of their excitotoxic properties (Olney, 1969 (Figure 1).…”

Quinoxalines interact with the glycine recognition site of NMDA receptors: studies in guinea‐pig myenteric plexus and in rat cortical membranes

“…* P <0.05 vs Glu alone; ** P < 0.01 vs. Glu alone; 'P < 0.05 vs. Glu + CNQX alone; bp < 0.01 vs. Glu + CNQX alone. (0) (Birch et al, 1988b;Blake et al, 1988;Fletcher et al, 1988;Honore et al, 1988). Our experiments, performed in the guinea-pig ileum myenteric plexus, which is a pharmacological preparation suitable for the study of molecules interacting both with the glutamate and the glycine recognition sites of the NMDA receptor ion channel complex (Moroni et al, 1986;Luzzi et al, 1988;Moroni et al, 1989;Reggiani et al, 1989) (Erez et al, 1985;Frey et al, 1988).…”

“…The quinoxalinediones, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, also known as FG9065) and 6,7, dinitroquinoxaline-2,3-dione (DNQX, FG9041), have been reported to be selective, potent and competitive antagonists for the quisqualate and the kainate subtypes of excitatory amino acid receptors (Honore' et al., 1988;Fletcher et al, 1988), and have therefore been proposed and utilized as powerful tools for detailed investigations on the physiological role of non N-methyl-D-aspartate (NMDA) receptors (Blake et al…”

“…The quinoxalinediones, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, also known as FG9065) and 6,7, dinitroquinoxaline-2,3-dione (DNQX, FG9041), have been reported to be selective, potent and competitive antagonists for the quisqualate and the kainate subtypes of excitatory amino acid receptors (Honore' et al, 1988;Fletcher et al, 1988), and have therefore been proposed and utilized as powerful tools for detailed investigations on the physiological role of non N-methyl-D-aspartate (NMDA) receptors (Blake et al, 1988;McBain et al, 1988;Andreasen et al, 1989;Davies et al, 1989;Harris, 1989 quantitative pharmacological studies have revealed that both CNQX and DNQX also block NMDA responses in a non-competitive manner, probably interacting with the strychnine-insensitive glycine modulatory site of NMDA receptors (Birch et al, 1988b;Foster, 1988; Verdoorn & Dingledine, 1988).…”

Possible roles ofl-phosphoserine in the pathogenesis of Alzheimer’s disease

“…A significant contribution of the NMDA competitive antagonist action of L-PSer is less likely because only a small component of synaptically evoked field potentials in the CAI hippocampal region are mediated by NMDA receptors in Mg2 -containing solutions (Andreasen et at,, 1989). The major portion of CAI population EPSP is mediated through non-NMDA receptors, i.e., AMPA/QA or KA receptors (Fletcher et at., 1988;Andreasen et a!., 1989). Considering this, the ability of L-PSer to block high-affinity KA binding may represent another mechanism through which this compound could inhibit CAI population EPSP, but the lack of effect on [ 3 H]AMPA binding makes this much less likely.…”