title: Serotonin 2A receptor antagonists for treatment of schizophrenia.
abstract: BACKGROUND
  All approved antipsychotic drugs share an affinity for the dopamine 2 (D(2)) receptor; however, these drugs only partially ameliorate the symptoms of schizophrenia. It is, therefore, of paramount importance to identify new treatment strategies for schizophrenia.
  
  
  METHODS
  Preclinical, clinical and post-mortem studies of the serotonin 5-HT(2A) system in schizophrenia are reviewed. The implications of a combined D(2) and 5-HT(2A) receptor blockade, which is obtained by several current antipsychotic drugs, are discussed, and the rationale for the development of more selective 5-HT(2A) receptor antagonists is evaluated. Moreover, the investigational pipeline of major pharmaceutical companies is examined and an Internet search conducted to identify other pharmaceutical companies investigating 5-HT(2A) receptor antagonists for the treatment of schizophrenia.
  
  
  CONCLUSIONS
  5-HT(2A) receptor antagonists appear to assume an intermediate position by being marginally superior to placebo but inferior to conventional antipsychotic drugs. Three previous 5-HT(2A) receptor antagonists have been discontinued after Phase II or III trials, and available Phase IIa data on the remaining 5-HT(2A) receptor antagonist will need substantial additional validation to be approved as a new treatment strategy against schizophrenia.
authors: Center for Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital Glostrup, Faculty of Health Sciences, Psychiatric Center Glostrup, Nordre Ringvej 29, DK-2600 Glostrup, Denmark.
authors: Bjørn H
authors: BH
authors: Ebdrup
authors: Hans
authors: H
authors: Rasmussen
authors: Jørn
authors: J
authors: Arnt
authors: Birte
authors: B
authors: Glenthøj
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005464:Fluorobenzenes / Q000627:therapeutic use; D006801:Humans; D010636:Phenols / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000627:therapeutic use*; D014508:Urea / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D005464:Fluorobenzenes; D010636:Phenols; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists; C076033:SR 46349B; D014508:Urea; C079049:volinanserin; C510793:pimavanserin