Attenuation of nociceptive responses by ACEA-1021, a competitive NMDA receptor/glycine site antagonist, in the mice.

Intrathecal administration of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists has been shown to produce antinociception in various animal models of pain. In the present study we examined the effect of 5-nitro-6,7-dichloro-1,4-dihydro-2,3-quinoxalinedione (ACEA-1021), a competitive NMDA receptor/glycine site antagonist, on nociceptive responses in the tail flick and formalin tests in mice. Swiss Webster mice were injected with ACEA-1021 intraperitoneally (1-60 mg/kg), or intrathecally (1-40 micrograms/mouse), and tested for antinociception. Systemic administration of ACEA-1021 attenuated the nociceptive responses solely in the formalin test. Nevertheless, intrathecal administration of ACEA-1021 showed equally potent attenuation of nociceptive responses in both animal models of pain. The effect of ACEA-1021 was also examined on caudally directed biting and scratching (CDBS) behaviors induced by intrathecal administration of NMDA. Microinjections of NMDA (1-1000 microM) in the spinal cord produced dose-dependent CDBS behaviors. Mice pretreated with ACEA-1021 (0.5-40 micrograms/mouse) showed dose-dependent protection against CDBS behaviors induced by intrathecal NMDA. Taken together, the results suggest that ACEA-1021 may block spinal NMDA receptors to attenuate nociceptive responses, however, our data cannot exclude the involvement of non-NMDA receptors.