Antinociception and less gastric injury with the dexketoprofen-tapentadol combination in mice

Fundam Clin Pharmacol. 2021 Apr;35(2):371-378. doi: 10.1111/fcp.12625. Epub 2020 Nov 17.

Abstract

The purpose of this study was to evaluate the antinociceptive interaction between dexketoprofen and tapentadol in three different dose ratios, as well as the ulcerogenic activity of this combination. Dose-response curves were carried out for dexketoprofen, tapentadol, and dexketoprofen-tapentadol combinations in the acetic acid-induced writhing test in mice. On the other hand, the gastric damage of all treatments was assessed after the surgical extraction of the stomachs. Intraperitoneal administration of dexketoprofen and tapentadol induced a dose-dependent antinociceptive effect, reaching a maximal effect of about 58% and 99%, respectively. Isobolographic analysis and the interaction index showed that the three proportions produced an analgesic potentiation (synergistic interaction). Interestingly, the 1:1 and 1:3 ratios of the drugs combination produced minor gastric injury in comparison with the 3:1 proportion. Our data suggest that all proportions of the dexketoprofen-tapentadol combination produced a synergistic interaction in the acetic acid-induced visceral pain model in mice with a low incidence of gastric injury.

Keywords: Isobolographic analysis; dexketoprofen; tapentadol; ulcerogenic effect; writhing assay.

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / adverse effects
  • Analgesics / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Drug Synergism
  • Ketoprofen / administration & dosage
  • Ketoprofen / adverse effects
  • Ketoprofen / analogs & derivatives*
  • Ketoprofen / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nociceptive Pain / prevention & control*
  • Pain Measurement
  • Stomach Ulcer / chemically induced
  • Tapentadol / administration & dosage
  • Tapentadol / adverse effects
  • Tapentadol / pharmacology*
  • Tromethamine / administration & dosage
  • Tromethamine / adverse effects
  • Tromethamine / pharmacology*

Substances

  • Analgesics
  • Drug Combinations
  • Tromethamine
  • Ketoprofen
  • Tapentadol
  • dexketoprofen trometamol