The Endocannabinoid System: A Dynamic Signalling System at the Crossroads Between Metabolism and Disease

摘要: The discovery of the endocannabinoid system (ECS) in early 1990s last century generated high expectations new therapeutic opportunities. Its central role and pleiotropic character seemed to offer promising indications fields pain, inflammation, CNS disorders, weight management metabolic diseases. However, around 2007 tide began turn when several cannabinoid receptor type 1 (CB1) antagonists/inverse agonists failed as therapeutics against overweight its complications. More recently, development FAAH (Fatty Acid Amide Hydrolase) inhibitors pain has also faced serious setbacks. In retrospect much greater complexity ECS than originally assumed played a fundamental these difficulties. Although there is no doubt that endocannabinoids their receptors are great (patho-)physiological relevance, it become clear intimately intertwined with other biological systems. Endocannabinoids exist equilibrium fatty acids derivatives, including eicosanoids prostamides. Furthermore, biologically active analogues endocannabinoids, particular acid amides, pathways overlapping those ECS. Finally, per se congeners show “promiscuous” behaviour going beyond interactions CB1 CB2 receptors. It what may be called “endocannabinoidome” demands for pharmacological approaches take into account dynamics. Targeting continues opportunities prevention therapy, chronic chances success more likely come from “multiple-target” “single-target” approaches.