benzofurans and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic-acid

The selective kappa-opioid receptor agonist CI-977, stereoselectively antagonised clonic seizures induced by slow i.v. infusion of N-methyl-DL-aspartate in the mouse. It was found to be more efficacious and 10-fold more potent than the competitive N-methyl-D-aspartic acid receptor antagonist CPP (3-(+/-)-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid). The anticonvulsant action of CI-977 was antagonised by norbinaltorphimine indicating a specific interaction with the kappa-receptor. The effect of CI-977 but not that of CPP was also antagonised by the glycine/NMDA receptor agonist D-serine. These results provide evidence for a possible interaction between the kappa-receptor and the glycine/NMDA receptor.

Topics: Animals; Anticonvulsants; Benzofurans; Dizocilpine Maleate; In Vitro Techniques; Mice; Mice, Inbred Strains; Naltrexone; Piperazines; Pyrrolidines; Radioligand Assay; Rats; Receptors, N-Methyl-D-Aspartate; Receptors, Opioid; Receptors, Opioid, kappa; Seizures; Stereoisomerism