title: Blockade of morphine tolerance by ACEA-1328, a novel NMDA receptor/glycine site antagonist.
abstract: Recent studies indicate that competitive and non-competitive NMDA receptor antagonists can block the development of morphine tolerance. Since glycine is considered to be a co-agonist for activation of NMDA receptors we examined the effect of a novel bioavailable NMDA receptor/glycine site antagonist, 5-nitro-6,7-dimethyl-1,4-dihydro-2,3-quinoxalinedione (ACEA-1328), on the development of morphine tolerance. Administration of ACEA-1328 (20 mg/kg) completely blocked tolerance to morphine-induced antinociception in the tail flick test in CD-1 mice, without affecting the basal nociceptive response or potentiating morphine-induced antinociceptive effects. These data suggest that inhibition of NMDA receptor activity via blockade of the glycine co-agonist site is potentially viable as a therapeutic approach for preventing development of morphine tolerance.
authors.affiliation: Department of Pharmacology, College of Medicine, University of California, Irvine 92717, USA.
authors.forename: K
authors.initials: K
authors.lastname: Lutfy
authors.forename: K Z
authors.initials: KZ
authors.lastname: Shen
authors.forename: I S
authors.initials: IS
authors.lastname: Kwon
authors.forename: S X
authors.initials: SX
authors.lastname: Cai
authors.forename: R M
authors.initials: RM
authors.lastname: Woodward
authors.forename: J F
authors.initials: JF
authors.lastname: Keana
authors.forename: E
authors.initials: E
authors.lastname: Weber
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004361:Drug Tolerance; D007700:Kinetics; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014981:Xenopus
chemical_list: C093392:ACEA 1328; D000700:Analgesics; D011810:Quinoxalines; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D009020:Morphine