Blockade of morphine tolerance by ACEA-1328, a novel NMDA receptor/glycine site antagonist

Kabirullah Lutfy, Ke Zhong Shen, Ik Sung Kwon, Sui Xiong Cai, Richard M. Woodward, John F.W. Keana, Eckard Weber

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)187-189
Number of pages3
JournalEuropean Journal of Pharmacology
Issue number1-2
StatePublished - Jan 24 1995


  • (CD-1 mouse)
  • Morphine tolerance
  • NMDA receptor/glycine site antagonist
  • Tail flick test

ASJC Scopus subject areas

  • Pharmacology


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