N-methyl-D-aspartate receptor antagonists potentiate morphine's antinociceptive effect in the rat

The interaction between morphine and three antagonists of the N-methyl-D-aspartate (NMDA) receptor. MK-801 (non-competitive channel blocker), dextromethorphan (clinically available non-competitive antagonist) and CGS19755 (competitive receptor antagonist), was examined in rats with the hot plate test. The NMDA antagonists were administered intraperitoneally and none of them caused antinociception at doses that did not produce motor deficits (0.1 mg kg-1 MK-801, 30 mg kg-1 dextromethorphan and 5 mg kg-1 CGS19755). However, pretreatment with the NMDA antagonists at these doses 30 min prior to subcutaneous injection of 5 mg kg-1 morphine significantly potentiated the antinociceptive effect of morphine, with strongest effect observed with dextromethorphan. It is suggested that blockade of NMDA receptors enhances the antinociceptive effect of morphine and NMDA antagonists may improve the analgesic efficacy of morphine in the clinic.