Atypical Antipsychotics and Inverse Agonism at 5-HT2 Receptors

作者：Sullivan Laura C; Clarke William P; Berg Kelly A^*

来源：Current Pharmaceutical Design, 2015, 21(26): 3732-3738.

DOI：10.2174/1381612821666150605111236

• Antipsychotic drugs
• atypical antipsychotic drugs
• inverse agonism
• constitutive activity
• serotonin
• 5-HT2A receptors
• 5-HT2C receptors
• schizophrenia

It is now well accepted that receptors can regulate cellular signaling pathways in the absence of a stimulating ligand, and inverse agonists can reduce this ligand-independent or "constitutive" receptor activity. Both the serotonin 5-HT2A and 5-HT2C receptors have demonstrated constitutive receptor activity in vitro and in vivo. Each has been identified as a target for the treatment of schizophrenia. Further, most, if not all, atypical antipsychotic drugs have inverse agonist properties at both 5-HT2A and 5-HT2C receptors. This paper describes our current knowledge of inverse agonism of atypical antipsychotics at 5-HT2A/2C receptor subtypes in vitro and in vivo. Exploiting inverse agonist properties of antipsychotic drugs may provide new avenues for drug development.

• 出版日期2015