Molecular diversity of the dopamine receptors.

Our current understanding of the relationship between the dopaminergic system and human brain disorders is based on two fundamental discoveries: dopamine-replacement herapy can alleviate Parkinson’s disease (1-3) and, secondly, many antipsychotic drugs are dopamine receptor antagonists (4-7). These discoveries have guided two major directions in dopamine-related basic research and drug design: to activate dopamine receptors left understimulated by the degeneration of the afferent dopamine-secreting cells and to prevent dopamine from binding to its receptor, according to the hypothesis that schizophrenia is the result of dopamine receptor overactivity (5, 8). Since blockade of the dopamine receptors (antipsychotic therapy) can lead to a state similar to that resulting from dopamine depletion (Parkinson’s therapy) and higher doses of dopamine can cause psychoses, the therapies of disorders resulting from dopamine imbalances are associated with adverse side effects. The ideal drug(s) that will treat one disorder without affecting the other has thus far not been found. However, the search for such a drug has led to the design of several dopamine receptor ligands that, in turn, have increased our understanding of the dopaminergic system. In particular, these studies have