Blockade of the polyamine site of NMDA receptors produces antinociception and enhances the effect of morphine, in mice.

The possible effect of ifenprodil--a potent antagonist at the polyamine site of the NMDA receptor complex--on nociceptive threshold and morphine analgesia was investigated in mice. In the hot plate test, the intraperitoneal (i.p.) injection of ifenprodil significantly prolonged the reaction time of mice at the dose of 30 mg/kg, and increased the analgesic effect of morphine. In the phenylquinone writhing test, ifenprodil reduced the number of abdominal constrictions of mice starting from the dose of 2.5 mg/kg i.p., and increased the effect of morphine. The effect of ifenprodil on pain threshold was prevented by naloxone. Moreover, ifenprodil antagonized the pain threshold-reducing effect of alpha-melanocyte-stimulating hormone (0.05 microgram/mouse, intracerebroventricularly). These data show that blockade of the polyamine site of the NMDA receptor complex produces analgesia and increases the analgesic effect of morphine.