d-Methadone is antinociceptive in the rat formalin test Journal Article
| Authors: | Shimoyama, N.; Shimoyama, M.; Elliott, K. J.; Inturrisi, C. E. |
| Article Title: | d-Methadone is antinociceptive in the rat formalin test |
| Abstract: | The l-isomer of methadone possesses opioid activity, whereas the d-isomer is weak or inactive as an opioid. Both d- and l-methadone have been shown to bind to the N-methyl-D-aspartate (NMDA) receptor. To determine whether d-methadone has functional, in vivo NMDA receptor antagonist activity, the antinociceptive effects of d-methadone were evaluated in the rat tail-flick and formalin tests. Cumulative dose-response analysis in the tail-flick test revealed an ED50 value far intrathecal (spinal) l-methadone of 15.6 mu g/rat. In contrast, spinal d-methadone produced no antinociception at a cumulative dose of 460 mu g/rat. d-Methadone in a dose range from 32 to 320 mu g/rat dose-dependently reduced formalin-induced flinching behavior during phase 2 but not during phase 1 of the formalin test. These antinociceptive effects of d-methadone were not blocked by a spinal dose of naloxone that effectively antagonized an antinociceptive (tail-flick test) dose of l-methadone. d-Methadone at an intrathecal dose of 250 mu g shifted the ED50 value for NMDA-induced nociceptive behaviors more than 3-fold to the right, which indicates an antagonism of these NMDA receptor-mediated effects. These results indicate that d-methadone is antinociceptive as a result of its NMDA receptor antagonist activity. |
| Keywords: | pain; ketamine; double-blind; spinal-cord; morphine-tolerance; receptor antagonists; tissue-injury; excitatory amino-acids; central sensitization; nmda antagonist |
| Journal Title: | Journal of Pharmacology and Experimental Therapeutics |
| Volume: | 283 |
| Issue: | 2 |
| ISSN: | 0022-3565 |
| Publisher: | American Society for Pharmacology and Experimental Therapeutics |
| Date Published: | 1997-11-01 |
| Start Page: | 648 |
| End Page: | 652 |
| Language: | English |
| ACCESSION: | WOS:A1997YF25400029 |
| PROVIDER: | wos |
| PUBMED: | 9353381 |
| Notes: | Article -- Source: Wos |
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