European journal of pharmacology
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Past studies have shown antagonists of excitatory amino acid receptors, both N-methyl-D-aspartate (NMDA) and non-NMDA, to produce an antinociceptive effect in vitro and in vivo. Additionally, NMDA receptor antagonists have been demonstrated to prevent morphine tolerance. We had found that one NMDA receptor antagonist, ketamine, potentiates morphine's analgesic effect in post-operative patients. ⋯ However, high-affinity sites in rats treated with D-AP5 and morphine displayed a higher affinity (KD = 0.45 +/- 0.09 nM) than those of control animals (KD = 0.95 +/- 0.08 nM). Results of this study indicate that competitive as well as non-competitive NMDA receptor antagonists enhance morphine's antinociceptive effect, and prevent the development of morphine tolerance. Thus, in our opinion, there opens a new frontier in clinical pain management, especially for those patients who require long-term opioid treatment for pain relief.