title: Inverse agonists - What do they mean for psychiatry?
abstract: The nomenclature of drugs is a critical aspect of science, since it can direct research and optimize treatment choices. Traditionally drugs acting on CNS receptors have been classified as either agonists or antagonists. Recently a new class of ligand, the inverse agonist, has been identified in some receptor systems. Inverse agonists have opposite actions to those of agonists but the effects of both of these can be blocked by antagonists. Pimavanserin is a new 5-HT2A receptor acting drug that has been given market authorization for psychosis in Parkinson׳s disease. The FDA have termed it an inverse agonist, but this conclusion is based on in-vitro data. In this paper we discuss the evidence for such a claim being made for pimavanserin in the human brain and conclude that this is not currently sufficient. It is therefore premature to conclude that the actions of pimavanserin in humans are due to inverse agonism, and we are of the opinion that it should be called a 5-HT2A antagonist until better evidence emerges.
authors.affiliation: Centre for Psychiatry, Imperial College London, UK. Electronic address: d.nutt@imperial.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Nutt
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Stahl
authors.affiliation: Institute of Mental Health Research, The Royal Mental Health Care Centre, Ottawa, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Blier
authors.affiliation: Biometec, University of Catania School of Medicine, Catania, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.affiliation: Department of Psychiatry, Sheba Medical Center & Sackler School of Medicine, Tel Aviv University, TelHashomer, Israel.
authors.forename: Joseph
authors.initials: J
authors.lastname: Zohar
authors.affiliation: Centre for Psychiatry, Imperial College London, UK.
authors.forename: Sue
authors.initials: S
authors.lastname: Wilson
mesh_terms: D000818:Animals; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy*; D010880:Piperidines / Q000627:therapeutic use; D058825:Serotonin 5-HT1 Receptor Agonists / Q000627:therapeutic use*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000627:therapeutic use*; D014508:Urea / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D010880:Piperidines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D014508:Urea; C510793:pimavanserin
keywords: 5-HT2A; Antagonist; Inverse agonist; Serotonin