title: Targeting 5-HT receptors for the treatment of obesity.
abstract: Serotonin is known to have anorectic properties through centrally acting mechanisms. Three serotonin receptors have been implicated in mediating these effects: 5-HT(1B), 5-HT(2C) and 5-HT(6). Hypophagic effects are elicited through agonism of the former two receptors, whereas antagonism of the 5-HT(6) receptor appears to have an anorectic effect. All three targets have been validated through extensive studies including knockout mice and selective ligand assessment. 5-HT(1B) receptor agonists have limited utility due to mechanism-based side effects, whereas 5-HT(2C) receptor agonists suffer from challenges associated with selectivity over the closely related 5-HT(2A) and 5-HT(2B) receptors. 5-HT(6) receptor antagonists appear to offer great promise, although the mechanisms through which they reduce food intake and body weight are not fully understood.
authors.affiliation: Discovery R&D, AMRI, 26 Corporate Circle, PO Box 15098, Albany, NY 12212-5098, United States. bruce.sargent@amriglobal.com
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Sargent
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Henderson
mesh_terms: D000818:Animals; D006801:Humans; D058990:Molecular Targeted Therapy; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin