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.
Stringer
M
M
Pain Research Institute, Clinical Sciences Centre, University Hospital Aintree, L9 7AL, Liverpool, UK.
Makin
M K
MK
Miles
J
J
Morley
J S
JS
D000701:Analgesics, Opioid / Q000378:metabolism*; D000818:Animals; D016291:Dizocilpine Maleate / Q000378:metabolism*; D009020:Morphine / Q000737:chemistry / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010146:Pain / Q000188:drug therapy / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013237:Stereoisomerism
D000701:Analgesics, Opioid; D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D016291:Dizocilpine Maleate; D009020:Morphine; D009638:Norepinephrine