Our understanding of the functional mechanisms relating dopamine activity to normal and abnormal behavior has been turned "upside-down" by the recent developments described in the chapters of this volume. Heretofore, it was generally agreed that all of the pharmacological and behavioral properties ascribed to dopamine systems were mediated via activation or inhibition of the subtype of dopamine receptors termed D2. The properties of these receptors were first characterized in 1975 following their identification by receptor binding techniques utilizing 3H-butyrophenones, potent antipsychotic drugs, used in the treatment of schizophrenia. Although another subtype of dopamine receptor had already been identified a few years earlier, now termed the Dl receptor, its functional properties were unknow- other than the fact that it was associated with the activation of the enzyme adenylate cyclase. Our absence of knowledge of the behavioral functions of this receptor stemmed primarily from the lack of selective agonist and antagonists for DI receptors - drugs which did not also interact with D2 receptors. Selective agents for D2 receptors did exist and hence the behavioral roles of D2 receptors were easily ascribed. The work described in this text is primarily stimulated by the development of two selective Dl receptor drugs - the antagonist SCH 23390 and the agonist SKF 38393. The studies described herein clearly show that D1 receptors do indeed have many behavioral functions, on the surface often similar to those responses mediated by D2 receptors.

The development of a selective D1 dopamine (DA) receptor antagonist SCH 23390 stimulated a number of studies on the functions mediated by central DA receptor subtypes. It was generally assumed that the central D1 DA receptor isa molecular entity whose function awaits further discovery. The papers presented in this volume clearly show that this is no longer the case and that D1 DA receptors have many behavioral fuctions which might be altered in pathological states. A number of papers have recognized the interdependence of the regulatory functions of the D1 DA receptors with D2 and other receptor proteins, and vice versa. The biochemical, pharmacological and morphological characterization of the D1 and D2 DA receptor binding proteins, as well as of DARPP-32, illustrates the complex interactions between various macromolecules. Procedures described for the purification of the D1 and D2 DA receptor subtypes are fundamental for future studies on the mechanisms involved in the coupling of the receptor proteins with signal transducing systems. Several studies in this volume show that D1 DA receptors have behavioral functions and that they are often similar to the responses mediated by D2 DA receptors, but in some instances reflect divergent neuronal activity of both systems. The knowledge of the physiology and biochemistry of the central DA receptor subtypes could lead to the development of a new generation of drugs which ameliorate some mental and neurological dysfunctions without producing severe undesirable side effects.

With contributions by numerous experts

This text presents the fundamentals of biochemistry and related topics for all those pursuing medical or other health-related fields such as clinical chemistry, medical technology, or pharmacology.

As sites of action for drugs used to treat schizophrenia and Parkinson’s disease, dopamine receptors are among the most validated drug targets for neuropsychiatric disorders. Dopamine receptors are also drug targets or potential targets for other disorders such as substance abuse, depression, Tourette’s syndrome, and attention deficit hyperactivity disorder. Updated from the successful first edition, "The Dopamine Receptors" serves as a reference work on dopamine receptors while also highlighting the areas of research that are most active today. To achieve this goal, authors have written chapters that set a broad area of research in its historical context, rather than focusing on the research output of their own laboratories.

LESLIE L. IVERSEN The present series of volumes is well timed, as the impact of molecular genetics on pharmacology has been profound, and a comprehensive review of the rapid advances of the past decade is much needed. Since the pioneering work of Dale, Ariens, and others in the early years of this century, much of pharmacology has been founded on the concept of receptors. To begin with, the receptor was conceived of as a "black box," which recognized and transduced the biological effects of neurotransmit ters, hormones, or other biological messengers-and which could also represent a target for man-made drugs. It is only in the last two decades that "molecular pharmacology" has blossomed, first with the advent of radioligand binding techniques and second messenger studies which greatly facilitated the biochemical study of drug-receptor interactions, and latterly with increasing knowledge of the molecular architecture of the receptor proteins themselves. This started with the traditional biochemical approach of isolating and purifying the receptor molecules. This proved to be a task of immense technical difficulty because of the low density of receptors in most biological source tissues, although there were some notable successes, e. g. , the purification of the nicotinic acetylcholine receptor from the electric organ of Torpedo. It was the ap plication of molecular genetics technology during the 1980s, however, which really accelerated progress in this field.