The 5-HT2C receptor as a target for mood disorders.
The serotonin (5-hydroxytryptamine<inf>2C</inf> [5-HT<inf>2C</inf>]) receptor is one of the 5-HT receptors with a G-protein-coupled intracellular signalling pathway. A large number of compounds showing antidepressive, antipsychotic and anxiolytic properties, and affecting sleep patterns, feeding behaviour and neuroendocrine functions, target this subtype of receptor. The potential use of 5-HT<inf>2C</inf> receptor ligands in psychiatry has been suggested as a result of a number of observations from animal and in vitro experiments. The results of studies performed suggest that some of the therapeutic effects of the selective serotonin re-uptake inhibitors (SSRIs) may be mediated, at least in part, by the 5-HT<inf>2C</inf> receptor. The long-term downregulation of 5-HT<inf>2C</inf> receptors is associated with their interaction with some SSRIs and may lead to disinhibition of the mesolimbic dopamine system, which may be partly responsible for their antidepressant action. Nevertheless, current evidence does not allow complete definition of 5-HT<inf>2C</inf> receptor functions and properties. Concerning genetics, there are no unequivocal results for the involvement of polymorphisms of the 5-HT<inf>2C</inf> receptor, and no studies on their association with an antidepressant response have ever been performed. This paper reviews some of the studies on this 5-HT receptor subtype, focusing on its possible importance as a target for mood disorder therapy.
Vita-Salute University, Department of Psychiatry, San Raffaele Hospital, Milano, Italy. serretti.alessandro@hsr.it
Alessandro
A
Serretti
Paola
P
Artioli
Diana
D
De Ronchi
D000818:Animals; D001921:Brain / Q000187:drug effects; D041321:Chromosomes, Human, X / Q000235:genetics; D015331:Cohort Studies; D015195:Drug Design; D011992:Endosomes / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D019964:Mood Disorders / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011619:Psychotropic Drugs / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D017393:RNA Editing / Q000187:drug effects; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C / Q000172:deficiency / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D017366:Serotonin Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011493:Protein Kinase C; D011619:Psychotropic Drugs; D044405:Receptor, Serotonin, 5-HT2C; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors