Pharmacological targeting of the serotonergic system for the treatment of obesity.
The attenuation of food intake as induced by an increase in serotonergic (5-hydroxytryptamine, 5-HT) efficacy has been a target of antiobesity pharmacotherapies. However, the induction of tolerance and/or side-effects limited the clinical utility of the earliest serotonin-related medications. With the global prevalence of obesity rising, there has been renewed interest in the manipulation of the serotonergic system as a point of pharmacological intervention. The serotonin(2C) receptor (5-HT(2C)R), serotonin(1B) (rodent)/serotonin(1Dbeta) (human) receptor (5-HT(1B/1Dbeta)R) and serotonin(6) receptor (5-HT(6)R) represent the most promising serotonin receptor therapeutic targets. Canonical serotonin receptor compounds have given way to a myriad of novel receptor-selective ligands, many of which have observable anorectic effects. Here we review serotonergic compounds reducing ingestive behaviour and discuss their clinical potential for the treatment of obesity.
Garfield
Alastair S
AS
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
Heisler
Lora K
LK
D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005277:Fenfluramine / Q000494:pharmacology; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology*; D011985:Receptors, Serotonin / Q000172:deficiency / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology*
D011985:Receptors, Serotonin; D018490:Serotonin Agents; D005277:Fenfluramine; D012701:Serotonin