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-HT_2A and 5-HT_2C 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-HT_2A and 5-HT_2C receptors. This paper describes our current knowledge of inverse agonism of atypical antipsychotics at 5-HT_2A/2C receptor subtypes in vitro and in vivo. Exploiting inverse agonist properties of APDs may provide new avenues for drug development.

Keywords: Antipsychotic drugs, atypical antipsychotic drugs, inverse agonism, constitutive activity, serotonin, 5-HT_2A receptors, 5-HT_2C receptors, schizophrenia.