Synergy between μ opioid ligands: Evidence for functional interactions among μ opioid receptor subtypes Journal Article
| Authors: | Bolan, E. A.; Tallarida, R. J.; Pasternak, G. W. |
| Article Title: | Synergy between μ opioid ligands: Evidence for functional interactions among μ opioid receptor subtypes |
| Abstract: | Pharmacological differences among μ opioid drugs have been observed in in vitro and in vivo preclinical models, as well as clinically, implying that all μ opioids may not be working through the same mechanism of action. Here we demonstrate analgesic synergy between L-methadone and several μ opioid ligands. Of the compounds examined, L-methadone selectively synergizes with morphine, morphine-6β-glucuronide, codeine, and the active metabolite of heroin, 6-acetylmorphine. Morphine synergizes only with L-methadone. In analgesic assays, D-methadone was inactive alone and did not enhance morphine analgesia when the two were given together, confirming that L-methadone was not acting through N-methyl-D-aspartate mechanisms. Both L-methadone and morphine displayed only additive effects when paired with oxymorphone, oxycodone, fentanyl, alfentanyl, or meperidine. Although it displays synergy in analgesic assays, the L-methadone/morphine combination does not exhibit synergy in the gastrointestinal transit assay. This analgesic synergy of L-methadone with selective μ opioid drugs and the differences in opioid-mediated actions suggest that these drugs may be acting via different mechanisms. These findings provide further evidence for the complexity of the pharmacology of μ opioids. |
| Keywords: | controlled study; unclassified drug; drug potentiation; nonhuman; mouse; animals; mice; animal experiment; animal model; dose-response relationship, drug; drug receptor binding; drug synergism; pethidine; drug mechanism; ligands; methadone; morphine; analgesics, opioid; pain measurement; analgesia; mu opiate receptor; receptors, opioid, mu; fentanyl; morphine 6 acetate; morphine 6 glucuronide; gastrointestinal transit; oxycodone; receptor subtype; codeine; oxymorphone; n methyl dextro aspartic acid; alfentanil; levomethadone; male; priority journal; article; dextro methadone |
| Journal Title: | Journal of Pharmacology and Experimental Therapeutics |
| Volume: | 303 |
| Issue: | 2 |
| ISSN: | 0022-3565 |
| Publisher: | American Society for Pharmacology and Experimental Therapeutics |
| Date Published: | 2002-11-01 |
| Start Page: | 557 |
| End Page: | 562 |
| Language: | English |
| DOI: | 10.1124/jpet.102.035881 |
| PUBMED: | 12388636 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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