Journal
EXPERT OPINION ON INVESTIGATIONAL DRUGS
Volume 20, Issue 9, Pages 1211-1223Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/13543784.2011.601738
Keywords
5-HT2A; CYR-101; drug development; eplivanserin; M100907; pimavanserin; schizophrenia; serotonin
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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-HT2A system in schizophrenia are reviewed. The implications of a combined D-2 and 5-HT2A receptor blockade, which is obtained by several current antipsychotic drugs, are discussed, and the rationale for the development of more selective 5-HT2A 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-HT2A receptor antagonists for the treatment of schizophrenia. Expert opinion: 5-HT2A receptor antagonists appear to assume an intermediate position by being marginally superior to placebo but inferior to conventional antipsychotic drugs. Three previous 5-HT2A receptor antagonists have been discontinued after Phase II or III trials, and available Phase IIa data on the remaining 5-HT2A receptor antagonist will need substantial additional validation to be approved as a new treatment strategy against schizophrenia.
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