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XB-ART-20182
Eur J Pharmacol 1995 Jan 24;2731-2:187-9. doi: 10.1016/0014-2999(94)00716-k.
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Blockade of morphine tolerance by ACEA-1328, a novel NMDA receptor/glycine site antagonist.

Lutfy K , Shen KZ , Kwon IS , Cai SX , Woodward RM , Keana JF , Weber E .


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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.

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