[Functional role of dopamine D4 receptor in schizophrenia]

D4 is the last receptor cloned among D2 receptor subtypes. Since clozapine has a high affinity to D4 receptors that exist abundantly in the hippocampus and frontal cortex, it is expected that the atypical clinical profiles of clozapine are associated with its blocking action to D4 receptors. Although D4 receptor functions have not been fully investigated, cognitive function of the brain may be associated with D4 receptors. D4 antagonists have only a weak inhibitory effect on the hyperactivity elicited by psychostimulants but induce no catalepsy or prolactin secretion. Previous positive studies on the elevation of the D4 receptors in the striatum of schizophrenia as well as on the association between D4 receptor polymorphism and schizophrenia have been followed by negative findings. Two D4 antagonists (L-745,879 and fananserine) failed to show clinical efficacy in schizophrenia. One of the major difficulties in D4 research is that no selective D4 ligands are available. Although D4 receptors may not play a major role in schizophrenia, they are expected to have a certain effect on frontotemporal function, such as cognition and negative symptoms of schizophrenia.