[Dopamine D4-receptor variants, schizophrenia and clozapine therapy]

Clozapine is an atypical antipsychotic with a low extrapyramidal side effect profile, and is often useful in the treatment of schizophrenics who do not respond to classical neuroleptics. While the dopamine D2-receptor is believed to be the primary target of classical neuroleptics, clozapine has greater affinity to the dopamine D4-receptor (DRD4). Great variability has been reported for the DRD4 gene and in the receptor itself. It is now possible to investigate if this variation influences individual differences in response to clozapine treatment or in the genetic susceptibility to schizophrenia. Till now the examined variations in the DRD4 gene do not seem to influence response to clozapine treatment or genetic susceptibility to schizophrenia. However, some of clozapine's side effects might be mediated through DRD4 binding.