title: Atypical antipsychotics and inverse agonism at 5-HT2 receptors.
abstract: It is now well accepted that receptors can regulate cellular signaling pathways in the absence of a stimulating ligand, and inverse agonists can reduce this ligand-independent or "constitutive" receptor activity. Both the serotonin 5-HT2A and 5-HT2C receptors have demonstrated constitutive receptor activity in vitro and in vivo. Each has been identified as a target for treatment of schizophrenia. Further, most, if not all, atypical antipsychotic drugs have inverse agonist properties at both 5-HT2A and 5-HT2C receptors. This paper describes our current knowledge of inverse agonism of atypical antipsychotics at 5-HT2A/2C receptor subtypes in vitro and in vivo. Exploiting inverse agonist properties of APDs may provide new avenues for drug development.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Sullivan
authors.forename: William P
authors.initials: WP
authors.lastname: Clarke
authors.affiliation: Department of Pharmacology - MS 7764, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. berg@uthscsa.edu.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Berg
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D055808:Drug Discovery; D054314:Drug Inverse Agonism; D006801:Humans; D008954:Models, Biological; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects* / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D044348:Receptors, Serotonin, 5-HT2; D058826:Serotonin 5-HT2 Receptor Agonists