title: The preclinical profile of asenapine: clinical relevance for the treatment of schizophrenia and bipolar mania.
abstract: BACKGROUND
  Asenapine is a novel antipsychotic drug approved for the treatment of acute schizophrenia, manic, or mixed episodes associated with bipolar I disorder, as a maintenance treatment of schizophrenia and as an adjunctive therapy with lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.
  
  
  METHODS
  This review focuses on the preclinical profile of asenapine. It analyzes the pharmacological, neurochemical, behavioral, and molecular mechanisms of asenapine and their contribution to the beneficial therapeutic advantages of the drug as reported in published preclinical and clinical studies, product labels, and poster presentations.
  
  
  CONCLUSIONS
  Asenapine exhibits a broad pharmacological profile that targets a wide range of neurotransmitter receptors with variable affinities. The drug preferentially increases dopamine, norepinephrine, and acetylcholine levels in cortical and limbic brain areas. It also potentiates cortical glutamatergic neurotransmission, and is active in behavioral animal models predictive of antipsychotic, antidepressant, and pro-cognitive activities. Chronic administration of asenapine alters the abundance of dopamine, serotonin, glutamate, adrenergic, and cholinergic receptor subtypes in different brain regions. These action mechanisms of asenapine might contribute to its unique psychopharmacological properties in the improved treatment of schizophrenia and other psychotic disorders.
authors.affiliation: Harvard Medical School and McLean Hospital, Department of Psychiatry and Neuroscience, Belmont, MA 02478, USA. ftarazi@hms.harvard.edu
authors.forename: Frank I
authors.initials: FI
authors.lastname: Tarazi
authors.forename: Jo C
authors.initials: JC
authors.lastname: Neill
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000378:metabolism; D003986:Dibenzocycloheptenes; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006576:Heterocyclic Compounds, 4 or More Rings / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D018377:Neurotransmitter Agents; C522667:asenapine