Mechanisms of Action of Atypical Antipsychotics

Abstract

AbstractAtypical antipsychotics—clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole—differ from conventional antipsychotics primarily by virtue of their actions at multiple central receptor sites. Each agent has its own unique receptor profile. The discovery of dopaminergic receptor-blocking capabilities of conventionblockingal antipsychotic drugs led to the dopamine hypothesis of schizophrenia. More recently, the role of serotonergic and other receptors in the pathophysiology and symptomology of schizophrenia and schizoaffective disorder has been identified, and the receptor actions of atypical antipsychotics have been linked to both antipsychotic efficacy and the propensity for extrapyramidal symptoms and other adverse effects. Receptor occupancy is directly related to antipsychotic dose, and the nature of the relationship between clinical utility and receptor occupancy is beginning to emerge. As our understanding of this relationship becomes more clear, the mechanism underlying clinical distinctions between agents will be understood.