d-Morphine, but not l-morphine, has low micromolar affinity for the non-competitive N-methyl-d-aspartate site in rat forebrain. Possible clinical implications for the management of neuropathic pain

A diverse range of opioids and enantiomers were examined for their ability to displace binding at the [(3)H] MK-801-labelled site of the N-methyl-D-aspartate (NMDA) receptor in rat forebrain, displacement which is equitable with non-competitive NMDA receptor antagonist activity. Surprisingly, d-morphine, but not natural l-morphine, has low micromolar affinity for the site, suggesting clinical potential for racemic dl-morphine in the treatment of neuropathic pain with reduced development of tolerance. The opioid mu-receptor agonists: levorphanol, d- and dl-methadone, displayed similar properties. With the exception of the case of d-morphine, the structural requirements for affinity correspond closely with those previously found for the inhibitory effects of opioids on monoamine uptake.