The anticonvulsant action of CI-977, a selective kappa-opioid receptor agonist: a possible involvement of the glycine/NMDA receptor complex.
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.
Singh
L
L
Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge, U.K.
Vass
C A
CA
Hunter
J C
JC
Woodruff
G N
GN
Hughes
J
J
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013237:Stereoisomerism
D000927:Anticonvulsants; D001572:Benzofurans; D010879:Piperazines; D011759:Pyrrolidines; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D016291:Dizocilpine Maleate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C067110:enadoline