Serotonin 2A receptor antagonists for treatment of schizophrenia.

Abstract

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.

• Authors: Bjørn H Ebdrup, Hans Rasmussen, Jørn Arnt, Birte Glenthøj
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 20 Issue 9 Pg. 1211-23 (Sep 2011) ISSN: 1744-7658 [Electronic] England
• PMID: 21740279 (Publication Type: Journal Article, Review)

Chemical References

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

Topics

• Antipsychotic Agents (therapeutic use)
• Brain (drug effects, 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, therapeutic use)