[Intrathecal co-administration of kappa opioid receptor agonists and NMDA receptor antagonists induces synergistic analgesia in rats].
It is reported that intrathecal (it) injection of low dose of dynorphin (Dyn) induces no analgesia while high dose of Dyn induces analgesia and might lead to hindlimb paralysis and loss of reflex via NMDA receptor. We hypothesized that NMDA receptor antagonists may reveal kappa analgesic-potential of subliminal dose of Dyn. Twenty-four hours after intrathecal cannulation, tail flick latency was measured before and after it of drugs. Combination of Dyn A- (1-13) 5 nmol or U50488H 100 nmol, a kappa receptor agonist with either DL-2-amino-5-phosphonovaleric acid (5 and 10 nmol) or kynurenic acid (25 and 50 nmol) it induced synergistic analgesia, which was reversed by nor-binaltorphimine 15 nmol, a kappa receptor antagonist. It is concluded that kappa opioid receptor agonists and NMDA receptor antagonists synergistically induce analgesia via interaction with their receptors.
Li
F C
FC
Department of Pharmacology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing.
Sun
X J
XJ
Hu
W H
WH
Jen
M F
MF
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D004399:Dynorphins / Q000494:pharmacology*; D007278:Injections, Spinal; D007736:Kynurenic Acid / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D000701:Analgesics, Opioid; D010446:Peptide Fragments; D011759:Pyrrolidines; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C026843:dynorphin (1-13); D004399:Dynorphins; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid