Title:Atypical antipsychotics and inverse agonism at 5-HT2 receptors
Volume: 21
Issue: 26
Author(s): Laura C. Sullivan, William P Clarke and Kelly A. Berg
Affiliation:
Keywords:
Antipsychotic drugs, atypical antipsychotic drugs, inverse agonism, constitutive activity, serotonin,
5-HT2A receptors, 5-HT2C receptors, schizophrenia.
Abstract: 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 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 APDs may provide new avenues for drug development.