title: The endocannabinoid signaling system: pharmacological and therapeutic aspects.
abstract: Since the discovery of anandamide in 1992, our knowledge of the endocannabinoid system and its physiological effects has increased greatly, not the least as a result of the availability of compounds affecting endocannabinoid function. In the present review, the pharmacology of the endocannabinoid system is discussed. At present, there are no compounds selectively inhibiting the synthesis of anandamide, and the mechanisms by which anandamide release and reuptake are blocked are a matter for current debate. In contrast, selective agonists and inverse agonists at the CB1 and CB2 receptors have been well characterised, as have inhibitors of the metabolism of anandamide by fatty acid amide hydrolase. Accumulating evidence has suggested that such compounds may be useful for the treatment of a number of disorders. With respect to the treatment of pain, topical CB1 agonists and CB2 agonists may prove therapeutically useful, and there is evidence that the non-steroidal inflammatory agent indomethacin produces effects secondary to activation of the endocannabinoid system. Modulation of the endocannabionid system may also produce neuroprotective effects, although present data would suggest that the observed effects are highly dependent upon the nature of the neurotoxic insult.
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, SE901 87 Umeå, Sweden. cf@pharm.umu.se
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fowler
authors.forename: Sandra
authors.initials: S
authors.lastname: Holt
authors.forename: Olov
authors.initials: O
authors.lastname: Nilsson
authors.forename: Kent-Olov
authors.initials: KO
authors.lastname: Jonsson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tiger
authors.forename: Stig O P
authors.initials: SO
authors.lastname: Jacobsson
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000096:biosynthesis / Q000502:physiology*; D063388:Endocannabinoids; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D018696:Neuroprotective Agents; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; C078814:anandamide