The dopamine D4 receptors and mechanisms of antipsychotic atypicality

The dopamine D4 receptor (D4) is a target for most common neuroleptic medications. After its initial discovery, it was found to possess the highest affinity of all dopamine receptor subtypes for the archetypical, atypical, antipsychotic clozapine. Nevertheless, initial clinical trials have not provided evidence that this receptor is a primary target for antipsychotic drugs. Considering the accumulated in vivo evidence that at least a subgroup of psychotic patients have altered dopamine signaling, all dopamine receptor subtypes likely contribute to the phenotypic expression of schizophrenia. New insights into the function of this receptor and its role in the modulation of excitatory signaling support the view that this dopamine receptor may affect attention and cognition. In this review, the authors outline some recent developments that provide insight into D4 receptor physiology, function and its possible relationship to schizophrenia treatment.