Comparison of the spinal anti-nociceptive effects of ES-242-1 and MK-801, two different NMDA antagonists, in rats

The purpose of this study was to determine whether ES-242-1, a novel N-methyl-D-aspartate (NMDA) receptor antagonist of microbial origin, has anti-nociception at the spinal level and to evaluate how its anti-nociceptive effect differs from that of MK-801, a non-competitive NMDA receptor antagonist. Agents were injected intrathecally (0.1, 1.0 and 10 microg) through a previously implanted PE tube in rats. Formalin (2%, 100 microl) was injected subcutaneously into the left hindpaw 15 min after each antagonist administration. Licking time as a nociceptive behavior was measured in three stages after formalin-injection, such as early phase (0-9 min), late first phase (10-29 min) and late second phase (30-60 min). In the early phase, the largest dose of ES-242-1 significantly decreased total licking time, although MK-801 did not show any significant reduction. With the treatment of 1.0 and 10 microg MK-801, total licking time in both late first and second phases was significantly suppressed, although the smallest dose (0.1 microg) of ES-242-1 showed a significant reduction in the late second phase. These results indicate that ES-242-1 is highly effective against tonic pain, such as inflammatory pain.