5-hydroxytryptamine medications for the treatment of obesity.
The central 5-hydroxytryptamine (5-HT; serotonin) system represents a fundamental component of the brain's control of energy homeostasis. Medications targeting the 5-HT pathway have been at the forefront of obesity treatment for the past 15 years. Pharmacological agents targeting 5-HT receptors (5-HTR), in combination with genetic models of 5-HTR manipulation, have uncovered a role for specific 5-HTRs in energy balance and reveal the 5-HT2 C R as the principal 5-HTR mediating this homeostatic process. Capitalising on this neurophysiological machinery, 5-HT2 C R agonists improve obesity and glycaemic control in patient populations. The underlying therapeutic mechanism has been probed using model systems and appears to be achieved primarily through 5-HT2 C R modulation of the brain melanocortin circuit via activation of pro-opiomelanocortin neurones signalling at melanocortin4 receptors. Thus, 5-HT2 C R agonists offer a means to improve obesity and type 2 diabetes, which are conditions that now represent global challenges to human health.
Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK.|Department of Pharmacology, University of Cambridge, Cambridge, UK.
L K
LK
Burke
Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK.
L K
LK
Heisler
D001066:Appetite / Q000187:drug effects; D001682:Biological Availability; D004734:Energy Metabolism; D006801:Humans; D009765:Obesity / Q000188:drug therapy*; D011333:Pro-Opiomelanocortin / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D058826:Serotonin 5-HT2 Receptor Agonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D058826:Serotonin 5-HT2 Receptor Agonists; D012701:Serotonin; D011333:Pro-Opiomelanocortin
5-HT2CR; lorcaserin; obesity; serotonin; type 2 diabetes