Current and Future Drug Targets in Weight Management 1799 Fig. 4 Some GPR119 ligands; the endogenous fatty acid amides oleylethanolamide (OEA) and N- oleoyldopamine (ODA), and two synthetic compounds : PSN632408 and AR-231453. arenapharm.com) and Ortho McNeil. It showed improve- ment of glucose control in diabetic patients. Nevertheless, the partners chose to give priority to the related compound APD-597 (structure not disclosed), which is now in phase I. Apparently, diabetes is the primary indication at this moment (73). Metabolex (www.metabolex.com) initiated a phase I trial with MBX-2982 (structure not disclosed) in March 2008; in November 2008, phase Ia data were presented. The drug was rapidly absorbed and showed a half-life allowing once- daily dosing. MBX-2982 also caused dose-dependent reduc- tions in glucose and increased GLP-1 following a mixed meal. The compound is now further developed together for diabetes with Sanofi-Aventis (74). OSI pharmaceuticals is currently in phase II with PSN-821. Taken together, study results with GPR119 agonists are encouraging. The Endocannabinoid System: Not a Lost Target The endocannabinoid system modulates food intake and energy metabolism at different levels, starting from recep- tors within the GI tract to the regulation of hedonic rewarding in the brain (33,75). It is regarded as a distinctive