Serotonin 2A receptor antagonists for treatment of schizophrenia

Expert Opin Investig Drugs. 2011 Sep;20(9):1211-23. doi: 10.1517/13543784.2011.601738. Epub 2011 Jul 8.


Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Publication types

  • Review

MeSH terms

  • Antipsychotic Agents / therapeutic use*
  • Brain / drug effects
  • Brain / metabolism
  • Fluorobenzenes / therapeutic use
  • Humans
  • Phenols / therapeutic use
  • Piperidines / therapeutic use
  • Positron-Emission Tomography
  • Receptor, Serotonin, 5-HT2A / drug effects
  • Schizophrenia / drug therapy*
  • Serotonin 5-HT2 Receptor Antagonists / therapeutic use*
  • Urea / analogs & derivatives
  • Urea / therapeutic use


  • Antipsychotic Agents
  • Fluorobenzenes
  • Phenols
  • Piperidines
  • Receptor, Serotonin, 5-HT2A
  • Serotonin 5-HT2 Receptor Antagonists
  • SR 46349B
  • Urea
  • volinanserin
  • pimavanserin