TY - JOUR

T1 - Serotonin 2A receptor antagonists for treatment of schizophrenia

AU - Ebdrup, Bjørn Hylsebeck

AU - Rasmussen, Hans

AU - Arnt, Jørn

AU - Glenthøj, Birte Yding

PY - 2011

Y1 - 2011

N2 - Introduction: All approved antipsychotic drugs share an affinity for the dopamine 2 (D2) 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 D2 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.

AB - Introduction: All approved antipsychotic drugs share an affinity for the dopamine 2 (D2) 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 D2 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.

U2 - 10.1517/13543784.2011.601738

DO - 10.1517/13543784.2011.601738

M3 - Journal article

C2 - 21740279

VL - 20

SP - 1211

EP - 1223

JO - Current Opinion in Investigational Drugs

JF - Current Opinion in Investigational Drugs

SN - 1354-3784

IS - 9

ER -