The anticonvulsant action of CI-977, a selective kappa-opioid receptor agonist: a possible involvement of the glycine/NMDA receptor complex

Eur J Pharmacol. 1990 Dec 4;191(3):477-80. doi: 10.1016/0014-2999(90)94183-x.

Abstract

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.

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Benzofurans / pharmacology*
  • Dizocilpine Maleate / pharmacology
  • In Vitro Techniques
  • Mice
  • Mice, Inbred Strains
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Piperazines / pharmacology
  • Pyrrolidines / pharmacology*
  • Radioligand Assay
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Receptors, Opioid / drug effects*
  • Receptors, Opioid, kappa
  • Seizures / chemically induced
  • Seizures / physiopathology
  • Stereoisomerism

Substances

  • Anticonvulsants
  • Benzofurans
  • Piperazines
  • Pyrrolidines
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • norbinaltorphimine
  • Naltrexone
  • Dizocilpine Maleate
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • enadoline