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-meth yl-D-aspartate (NMDA) receptor antagonist of microbial origin, has anti-noc iception at the spinal level and to evaluate how its anti-nociceptive effec t differs from that of MK-801, a non-competitive NMDA receptor antagonist. Agents were injected intrathecally (0.1, 1.0 and 10 mug) through a previous ly implanted PE tube in rats. Formalin (2%, 100 mul) was injected subcutane ously into the left hindpaw 15 min after each antagonist administration. Li cking time as a nociceptive behavior was measured in three stages after for malin-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 o f 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 mug MK -801, total licking time in both late first and second phases was significa ntly suppressed, although the smallest dose (0.1 mug) 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 . (C) 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.