title: New therapeutic opportunities for 5-HT2C receptor ligands in neuropsychiatric disorders.
abstract: The 5-HT2C receptor (R) displays a widespread distribution in the CNS and is involved in the action of 5-HT in all brain areas. Knowledge of its functional role in the CNS pathophysiology has been impaired for many years due to the lack of drugs capable of discriminating among 5-HT2R subtypes, and to a lesser extent to the 5-HT1B, 5-HT5, 5-HT6 and 5-HT7Rs. The situation has changed since the mid-90s due to the increased availability of new and selective synthesized compounds, the creation of 5-HT2C knock out mice, and the progress made in molecular biology. Many pharmacological classes of drugs including antipsychotics, antidepressants and anxiolytics display affinities toward 5-HT2CRs and new 5-HT2C ligands have been developed for various neuropsychiatric disorders. The 5-HT2CR is presumed to mediate tonic/constitutive and phasic controls on the activity of different central neurobiological networks. Preclinical data illustrate this complexity to a point that pharmaceutical companies developed either agonists or antagonists for the same disease. In order to better comprehend this complexity, this review will briefly describe the molecular pharmacology of 5-HT2CRs, as well as their cellular impacts in general, before addressing its central distribution in the mammalian brain. Thereafter, we review the preclinical efficacy of 5-HT2C ligands in numerous behavioral tests modeling human diseases, highlighting the multiple and competing actions of the 5-HT2CRs in neurobiological networks and monoaminergic systems. Notably, we will focus this evidence in the context of the physiopathology of psychiatric and neurological disorders including Parkinson's disease, levodopa-induced dyskinesia, and epilepsy.
authors.affiliation: Department of Physiology & Biochemistry, Faculty of Medicine and Surgery, University of Malta; Neuroscience Division, School of Biosciences, Cardiff University, Cardiff, UK. Electronic address: giuseppe.digiovanni@um.edu.mt.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Giovanni
authors.affiliation: Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5293) 33076 Bordeaux Cedex, France. Electronic address: deurwaer@u-bordeaux2.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: De Deurwaerdère
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D018377:Neurotransmitter Agents / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D008024:Ligands; D018377:Neurotransmitter Agents; D044405:Receptor, Serotonin, 5-HT2C
keywords: 5-HT receptors; Dopamine; G protein coupled receptors; GABA; Receptor oligomers; mRNA editing