title: 5-HT(2C) agonists as therapeutics for the treatment of schizophrenia.
abstract: The 5-HT(2C) receptor is a highly complex, highly regulated receptor which is widely distributed throughout the brain. The 5-HT(2C) receptor couples to multiple signal transduction pathways leading to engagement of a number of intracellular signaling molecules. Moreover, there are multiple allelic variants of the 5-HT(2C) receptor and the receptor is subject to RNA editing in the coding regions. The complexity of this receptor is further emphasized by the studies suggesting the utility of either agonists or antagonists in the treatment of schizophrenia. While several 5-HT(2C) agonists have demonstrated clinical efficacy in obesity (lorcaserin, PRX-000933), the focus of this review is on the therapeutic potential of 5-HT(2C) agonists in schizophrenia. To this end, the preclinical profile of 5-HT(2C) agonists from a neurochemical, electrophysiological, and a behavioral perspective is indicative of antipsychotic-like efficacy without extrapyramidal symptoms or weight gain. Recently, the selective 5-HT(2C) agonist vabicaserin demonstrated clinical efficacy in a Phase II trial in schizophrenia patients without weight gain and with low EPS liability. These data are highly encouraging and suggest that 5-HT(2C) agonists are potential therapeutics for the treatment of psychiatric disorders.
authors.affiliation: Pfizer Worldwide Research and Development, Groton, CT, USA. srlipson@gmail.com
authors.forename: Sharon
authors.initials: S
authors.lastname: Rosenzweig-Lipson
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Comery
authors.forename: Karen L
authors.initials: KL
authors.lastname: Marquis
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gross
authors.forename: John
authors.initials: J
authors.lastname: Dunlop
mesh_terms: D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use; D006801:Humans; D017393:RNA Editing; D012559:Schizophrenia / Q000188:drug therapy*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000627:therapeutic use*; D057170:Translational Research, Biomedical
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D058826:Serotonin 5-HT2 Receptor Agonists; C556517:vabicaserin