The effect of opioid antagonists on synergism between dexketoprofen and tramadol

C. Zegpi, C. Gonzalez, G. Pinardi, H. F. Miranda

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


The antinociceptive activity of dexketoprofen was studied in mice using the formalin assay for orofacial pain. The interaction between dexketoprofen and co-administered tramadol was studied using isobolographic analysis. The intraperitoneal administration of dexketoprofen or tramadol, showed dose-dependent antinociceptive activity in both phases of the assay. When administered together, the interaction was mildly synergistic during the first phase, and antagonistic in the second phase. Selective opioid receptor antagonists where used in order to measure the analgesic activity of tramadol in other regions of the CNS. The co-administration of dexketoprofen and tramadol, with previous administration of naltrexone, showed high synergistic activity during the first phase, and less but still synergistic during the second. When using naltrindole, the interaction was mildly more synergistic than the mixture dexketoprofen + tramadol during both phases. Using norbinaltorphimine, the interaction was synergistic in both phases, more marked in the second. These results suggest that the opioid activity of tramadol has an inhibiting effect in antinociceptive activity of the interaction between dexketoprofen and tramadol during the inflammatory (late) stages of pain.

Original languageEnglish
Pages (from-to)291-295
Number of pages5
JournalPharmacological Research
Issue number4
Publication statusPublished - Oct 2009


  • Dexketoprofen
  • Opioid antagonists
  • Orofacial formalin test
  • Synergism
  • Tramadol

ASJC Scopus subject areas

  • Pharmacology


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