Comparison of sigma- and kappa-opiate receptor ligands as excitatory amino acid antagonists.
Using the technique of microelectrophoresis in pentobarbitone-anaesthetized cats and rats, the effects of benzomorphans, with known actions at sigma- and kappa- opioid receptors, were tested on responses of spinal neurones to amino acids and acetylcholine. The racemic mixture and both enantiomers of the sigma opiate receptor agonist, N-allylnormetazocine (SKF 10, 047), and the dissociative anaesthetic, ketamine, reduced or abolished excitation evoked by N-methyl-aspartate (NMA) with only small and variable effects on responses to quisqualate or kainate. (+)-SKF 10, 047 was 1.2 +/- 0.7 times more potent than the (-)-enantiomer in antagonizing NMA. On Renshaw cells, (+)-SKF 10, 047 enhanced responses to acetylcholine whereas the (-) enantiomer produced only a small reduction. The kappa- opiate receptor agonist, ethylketocyclazocine, had no selective effects on responses to amino acids or to acetylcholine. We conclude that actions at sigma- but not kappa-, opiate receptors are responsible for the NMA antagonism observed with benzomorphans.
D000109:Acetylcholine / Q000494:pharmacology; D000596:Amino Acids / Q000037:antagonists & inhibitors*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D002415:Cats; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D016314:Ethylketocyclazocine; D007608:Kainic Acid / Q000037:antagonists & inhibitors; D007649:Ketamine / Q000494:pharmacology; D008024:Ligands; D008839:Microelectrodes; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects; D010069:Oxadiazoles / Q000037:antagonists & inhibitors; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D016318:Quisqualic Acid; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa; D017480:Receptors, sigma; D013237:Stereoisomerism
D000596:Amino Acids; D008024:Ligands; D010069:Oxadiazoles; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017480:Receptors, sigma; D001224:Aspartic Acid; D016314:Ethylketocyclazocine; D016202:N-Methylaspartate; D007649:Ketamine; C012134:SK&F 10047; D016318:Quisqualic Acid; D010620:Phenazocine; D003496:Cyclazocine; D000109:Acetylcholine; D007608:Kainic Acid