Brain dopamine D(4) receptors: basic and clinical status.

Since their discovery in 1991, an extraordinary amount of information has accumulated about the neurobiology and pharmacology of D(4) receptors in the mammalian central nervous system, making it timely to review salient aspects of this rapidly evolving research story and its relevance to clinical neuroscience. Recent progress in the molecular, genetic, anatomical, and functional characterization of D(4) receptors in the animal and human brain is yielding insights into their neurochemical and physiological roles in brain function. The temporal patterns of postnatal D(4) receptor development appear to differ in specific regions of mammalian forebrain. Postmortem neuropathological and clinical genetic studies have generally been disappointing regarding possible relationships of D(4) receptors to the pathophysiology or treatment of schizophrenia, however, they suggest relationships to other neuropsychiatric conditions, including attention deficit hyperactivity disorder, mood disorders, and Parkinson's disease. Several selective agonists and antagonists for D(4) receptors have been developed. Some are employed as experimental D(4) probes. The potential of D(4)-selective ligands as innovative treatments for neuropsychiatric disorders requires further investigation.