Synergistic antinociception by the cannabinoid receptor agonist anandamide and the PPAR-alpha receptor agonist GW7647

Roberto Russo, Jesse LoVerme, Giovanna La Rana, Giuseppe D'Agostino, Oscar Sasso, Antonio Calignano, Daniele Piomelli

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The analgesic properties of cannabinoid receptor agonists are well characterized. However, numerous side effects limit the therapeutic potential of these agents. Here we report a synergistic antinociceptive interaction between the endogenous cannabinoid receptor agonist anandamide and the synthetic peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist 2-(4-(2-(1-Cyclohexanebutyl)-3-cyclohexylureido)ethyl)phenylthio)-2-methylpropionic acid (GW7647) in a model of acute chemical-induced pain. Moreover, we show that anandamide synergistically interacts with the large-conductance potassium channel (KCa1.1, BK) activator isopimaric acid. These findings reveal a synergistic interaction between the endocannabinoid and PPAR-alpha systems that might be exploited clinically and identify a new pharmacological effect of the BK channel activator isopimaric acid.
Original languageEnglish
Pages (from-to)117-119
Number of pages3
JournalEuropean Journal of Pharmacology
Volume566
Issue number1-3
Early online date19 Mar 2007
DOIs
Publication statusPublished - 2 Jul 2007

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Keywords

  • Analgesics
  • Animals
  • Arachidonic Acids
  • Behavior, Animal
  • Butyrates
  • Cannabinoid Receptor Agonists
  • Drug Synergism
  • Endocannabinoids
  • Formaldehyde
  • Male
  • Mice
  • PPAR alpha
  • Pain
  • Phenylurea Compounds
  • Polyunsaturated Alkamides
  • Cannabinoid
  • Palmitoylethanolamide
  • Isopimaric acid
  • Formalin

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