Synergistic antinociception by the cannabinoid receptor agonist anandamide and the PPAR-alpha receptor agonist GW7647.
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.
Russo
Roberto
R
Department of Experimental Pharmacology, University of Naples, Naples, Italy.
LoVerme
Jesse
J
La Rana
Giovanna
G
D'Agostino
Giuseppe
G
Sasso
Oscar
O
Calignano
Antonio
A
Piomelli
Daniele
D
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists; D004357:Drug Synergism; D063388:Endocannabinoids; D005557:Formaldehyde; D008297:Male; D051379:Mice; D047493:PPAR alpha / Q000819:agonists*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*
D000700:Analgesics; D001095:Arachidonic Acids; D002087:Butyrates; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; C453899:GW 7647; D047493:PPAR alpha; D010671:Phenylurea Compounds; D053284:Polyunsaturated Alkamides; D005557:Formaldehyde; C078814:anandamide