Comparison of s‐ and κ‐ opiate receptor ligands as excitatory amino acid antagonists

Abstract

Using the technique of microelectrophoresis in pentobarbitone‐anaesthetized cats and rats, the effects of benzomorphans, with known actions at s‐ and κ‐ 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 κ‐ opiate receptor agonist, ethylketocyclazocine, had no selective effects on responses to amino acids or to acetylcholine. We conclude that actions at s‐ but not κ‐, opiate receptors are responsible for the NMA antagonism observed with benzomorphans.