Inhibitors of monoacylglycerol lipase as novel analgesics.
2-Arachidonoylglycerol (2-AG) is an endogenous cannabinoid (endocannabinoid) lipid whose functions remain poorly understood. Guindon and colleagues report the novel finding that exogenous application of 2-AG induces peripheral antinociceptive effects that are mediated, at least in part, by actions at peripheral cannabinoid CB(2) receptors. URB602, a recently described inhibitor of monoacylglycerol lipase, an enzyme that catalyzes 2-AG hydrolysis in vivo, also induced peripheral antinociceptive effects and enhanced the actions of 2-AG. Peripheral analgesic mechanisms represent promising therapeutic targets for suppressing pain in the absence of unwanted central nervous system side-effects (e.g. psychoactivity) associated with activation of central CB(1) receptors. The therapeutic potential of inhibitors of 2-AG deactivation for the treatment of inflammatory pain is discussed.
Hohmann
A G
AG
Neuroscience and Behavior Program, Department of Psychology, University of Georgia, Athens, GA 30602-3013, USA. ahohmann@uga.edu
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005989:Glycerides / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors*; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D001095:Arachidonic Acids; D001713:Biphenyl Compounds; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D005989:Glycerides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C501835:URB602; C094503:glyceryl 2-arachidonate; D008994:Monoacylglycerol Lipases