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

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.

• Authors: Roberto Russo, Jesse LoVerme, Giovanna La Rana, Giuseppe D'Agostino, Oscar Sasso, Antonio Calignano, Daniele Piomelli
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 566 Issue 1-3 Pg. 117-9 (Jul 02 2007) ISSN: 0014-2999 [Print] Netherlands
• PMID: 17434479 (Publication Type: Journal Article)

Chemical References

• Analgesics
• Arachidonic Acids
• Butyrates
• Cannabinoid Receptor Agonists
• Endocannabinoids
• GW 7647
• PPAR alpha
• Phenylurea Compounds
• Polyunsaturated Alkamides
• Formaldehyde
• anandamide

Topics

• Analgesics (pharmacology)
• Animals
• Arachidonic Acids (pharmacology)
• Behavior, Animal (drug effects)
• Butyrates (pharmacology)
• Cannabinoid Receptor Agonists
• Drug Synergism
• Endocannabinoids
• Formaldehyde
• Male
• Mice
• PPAR alpha (agonists)
• Pain (chemically induced, drug therapy, physiopathology)
• Phenylurea Compounds (pharmacology)
• Polyunsaturated Alkamides (pharmacology)