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
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Animals
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Anticonvulsants / pharmacology*
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Benzofurans / pharmacology*
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Dizocilpine Maleate / pharmacology
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In Vitro Techniques
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Mice
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Mice, Inbred Strains
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Naltrexone / analogs & derivatives
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Naltrexone / pharmacology
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Piperazines / pharmacology
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Pyrrolidines / pharmacology*
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Radioligand Assay
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Rats
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / drug effects*
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Receptors, Opioid / drug effects*
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Receptors, Opioid, kappa
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Seizures / chemically induced
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Seizures / physiopathology
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Stereoisomerism
Substances
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Anticonvulsants
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Benzofurans
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Piperazines
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Pyrrolidines
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Receptors, N-Methyl-D-Aspartate
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Receptors, Opioid
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Receptors, Opioid, kappa
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norbinaltorphimine
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Naltrexone
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Dizocilpine Maleate
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3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
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enadoline