Brain dopamine receptors: A primer on their current status, basic and clinical

Recent progress in understanding the molecular biology and pharmacology of dopamine receptors in mammalian brain has been remarkable and can serve as a basis for psychiatrically relevant research. The most prevalent central dopaminergic receptors, types D-1 and D-2, have been cloned, and their gene and peptide sequences and structures have been proposed. Novel gene products that resemble either D-1 (D-5) or D-2 (D-3, D-4) receptors also have been identified, their tissue distributions described, and their pharmacology characterized, mainly in gene-transfected cultured cells. These receptors belong to a superfamily of membrane proteins with seven membrane-spanning regions and an intracytoplasmic segment that interacts with G-proteins and other molecular elements of neurotransmission effector systems. Progress has been made toward developing agonists and antagonists for specific dopamine receptors. Recent discoveries have greatly stimulated clinical studies in neurogenetics, neuropathophysiology, and neuroradiology, New knowledge of receptor and effector components of brain dopaminergic neurotransmission systems is yielding revolutionary insights into the complexity of molecular neurotransmission. Innovative models for the rational design of novel neuropsychotropic agents and for seeking pathoetiologic contributions to major psychiatric and neurological disorders are anticipated. The discovery and definition of new gene products now require long-term efforts to clarify their physiology and to develop a pharmacology of novel dopamine receptors and their effectors.