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

Abstract

Using the technique of microelectrophoresis in pentobarbitone-anesthetized cats and rats, the effects of benzomorphans, with known actions at .sigma.- and .kappa.- opioid receptors, were tested on responses of spinal neurons 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 anesthetic, 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. Actions at .sigma.- but not .kappa.-, opiate receptors are evidently responsible for the NMA antagonism observed with benzomorphans.