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)


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
Issue number1-3
Early online date19 Mar 2007
Publication statusPublished - 2 Jul 2007



  • 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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