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Published on: September 23, 2015
Serotonin 2A receptor antagonists for treatment of schizophrenia
Bjørn H Ebdrup1, Hans Rasmussen, Jørn Arnt
1Center for Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital Glostrup, Faculty of Health Sciences, Psychiatric Center Glostrup, Nordre Ringvej 29, DK-2600 Glostrup, Denmark.
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.
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