Rehashing endocannabinoid antagonists: can we selectively target the periphery to safely treat obesity and type 2 diabetes?
A growing body of evidence supports an important role for the endocannabinoid system as a regulator of appetite, body weight, and systemic metabolism, which is overactive in obesity and type 2 diabetes. While initial attempts to target this system using the cannabinoid receptor inverse agonist rimonabant were successful in producing modest weight loss and improving obesity-related metabolic complications in humans, adverse central nervous system side effects precluded introduction of this drug into clinical practice. However, new data, presented by Tam and colleagues in this issue of the JCI, demonstrate that selective blockade of peripheral cannabinoid receptors may be a novel successful therapeutic approach.
Patti
Mary-Elizabeth
ME
Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215, USA. mary.elizabeth.patti@joslin.harvard.edu
D000818:Animals; D001069:Appetite Regulation; D001835:Body Weight; D063385:Cannabinoid Receptor Modulators / Q000037:antagonists & inhibitors* / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D063388:Endocannabinoids; D006801:Humans; D051379:Mice; D009765:Obesity / Q000188:drug therapy*; D010880:Piperidines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant