Isobolographic Analysis of the Interaction Between Tapentadol and Ketorolac in a Mouse Model of Visceral Pain

Drug Dev Res. 2016 Jun;77(4):187-91. doi: 10.1002/ddr.21310. Epub 2016 May 12.

Abstract

Preclinical Research The aim of this experimental assay was to assess the antinociceptive interaction between tapentadol and ketorolac in the acetic acid-induced writhing model in mice. Tapentadol (5.62-31.6 mg/kg ip) or ketorolac (5.62-31.6 mg/kg ip) were administered 15 min before the acetic acid administration. The ED50 values of the individual drugs were determined and different proportions (tapentadol-ketorolac in 1:1, 3:1, and 1:3) were assayed in combination in the writhing test. Isobolographic analysis and the interaction index demonstrated an antinociceptive synergistic interaction between tapentadol and ketorolac in all combination. Thus, the experimental ED50 values were lower when compared with their theoretical ED50 values. These data suggest that the tapentadol-ketorolac combination produces an antinociceptive synergistic interaction in the mouse acetic acid-induced writhing model. Drug Dev Res 77 : 187-191, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: acute visceral pain test; isobolographic analysis; ketorolac; tapentadol.

MeSH terms

  • Acetic Acid / toxicity
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Ketorolac / administration & dosage
  • Ketorolac / pharmacology*
  • Male
  • Mice
  • Phenols / administration & dosage
  • Phenols / pharmacology*
  • Tapentadol
  • Visceral Pain / drug therapy*
  • Visceral Pain / pathology

Substances

  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Phenols
  • Tapentadol
  • Acetic Acid
  • Ketorolac