DOPAMINE D-4 RECEPTORS - A NEW OPPORTUNITY FOR RESEARCH ON SCHIZOPHRENIA

Classically, the D-2 receptors formed the Gore of the dopamine hypothe sis for schizophrenia. Recently, the dopamine D-4 receptors have recei ved particular attention in this context. This is due to the atypical antipsychotic, clozapine, which is effective in treating refractory sc hizophrenics without the side-effect profile of typical neuroleptics, and displays a ten-fold higher affinity for D-4 compared to D-2 or D-3 receptors. Following various reports presenting the interest of D-4 r eceptors in treating schizophrenia, multiple chemical developments wer e made. During the last five years, various structures were described with a high selectivity for D-4 receptor subtype. Currently, although the first clinical report was very disappointing, the observation whic h support the idea that D-4 might serve as a target for clozapine have significantly modified and extended the understanding of mechanism un derlying atypical antipsychotic treatment of schizophrenia.