Serotonin Receptors And Transporters Exploring New And Known Signaling Pathways To Improve The Efficacy Of Antidepressant Treatment

The Advances in Pharmacology series presents a variety of chapters from the best authors in the field. Includes the authority and expertise of leading contributors in pharmacology Presents the latest release in the Advances in Pharmacology series

This book brings together an international group of clinicians and researchers from a broad swath of inter-related disciplines to offer the most up-to-date information about clinical and preclinical research into ketamine and second-generation “ketamine-like” fast-acting antidepressants. Currently available antidepressant medications act through monoaminergic systems, are ineffective for many individuals suffering from depression, and are associated with a delayed onset of peak efficacy of several months. The unexpected emergence of ketamine, an anesthetic N-methyl-D-aspartate (NMDA) receptor antagonist, as a rapid-acting antidepressant has reinvigorated CNS drug discovery research and catalyzed investigation in patient populations historically ignored in antidepressant drug development programs, particularly treatment-resistant patients and those with suicidality. Recent industry and academic research efforts have coalesced to explore NMDA receptor and glutamatergic molecular targets that lack ketamine’s psychotomimetic side effects and abuse liability but retain its rapid onset of efficacy. However, many fundamental questions remain regarding the neurobiological mechanisms underlying ketamine’s rapid antidepressant effects and the puzzling persistence of benefits observed in some patients following a single dose. This book examines how insights from these studies are forging new conceptual models of the neurobiology of stress-related affective, anxiety, and addictive disorders and the nature of treatment resistance. It also discusses how ketamine’s rapid antidepressant effects provide a scientific platform to facilitate innovation in clinical trial designs pertaining to patient selection, choice of control group, outcome measures, and dose-optimization. This book brings together data and insights from this rapidly expanding and extraordinarily promising field of study. Readers will be able to extract integrated themes and useful insights from the material contained in these diverse chapters and appreciate the paradigm-shifting contributions of ketamine to modern psychiatry and clinical neuroscience research.

Fluoxetine, best known by the trade name Prozac®, unlike other psychotropic drugs whose effects were serendipitously stumbled upon, was the first developed for a precise mechanism of action, that is, the ability to selectively inhibit serotonin reuptake, based upon the theory that increasing the availability of serotonin would treat major depression. Once approved by the FDA in 1987, fluoxetine quickly became the most prescribed psychotropic drug worldwide and its success in improving mood disorders has triggered the development of a large number of congener molecules, commonly known as SSRIs after their purported mechanism of action. However, a quarter of a century after its development, the idea that fluoxetine asserts its positive behavioral effect through inhibition of serotonergic reuptake is not firmly established. This book reviews several preclinical and clinical reports suggesting that the pharmacological effects of fluoxetine may be mediated by means other than the regulation of serotonin, including the regulation of gene expression, modifying epigenetic mechanisms as well as modifying microRNAs. One of the most prominent mechanisms for the therapeutic relevance of fluoxetine relates to influencing neuroplasticity by enhancing neurotropic factors, including BDNF signaling and altering adult neurogenesis. The ability of fluoxetine to rapidly increase neurosteroid levels accounts for the fast anxiolytic effects of this drug. Fluoxetine action at sigma-1 receptor or modulating glutamatergic neurotransmission as well as the combination of fluoxetine with other psychotropic drugs is discussed in relation to its therapeutic effects. While fluoxetine was primarily prescribed as an antidepressant, this drug currently represents a treatment of choice for a broad spectrum of psychiatric disorders, including post-traumatic stress disorder and a range of anxiety disorders. This drug even possesses analgesic actions and is a valuable therapy for stroke. This book also highlights emerging evidence on the gender-specific effects of fluoxetine, its potential adverse features, including its addiction liability in combination with psychostimulants, and the impact of perinatal fluoxetine exposure.

This book provides a reference guide describing the current status of medication in all major psychiatric and neurological indications, together with comparisons of pharmacological treatment strategies in clinical settings in Europe, USA, Japan and China. In addition, it highlights herbal medicine as used in China and Japan, as well as complementary medicine and nutritional aspects. This novel approach offers international readers a global approach in a single dedicated publication and is also a valuable resource for anyone interested in comparing treatments for psychiatric disorders in three different cultural areas. There are three volumes devoted to Basic Principles and General Aspects, offering a general overview of psychopharmacotherapy (Vol. 1); Classes, Drugs and Special Aspects covering the role of psychotropic drugs in the field of psychiatry and neurology (Vol. 2) and Applied Psychopharmacotherapy focusing on applied psychopharmacotherapy (Vol. 3). These books are invaluable to psychiatrists, neurologists, neuroscientists, medical practitioners and clinical psychologists.

A comprehensive review of the current status of antidepressants - how we arrived at this point in their evolution and where we are going in both the near and the long term. It employs both a scientific and historical approach to accomplish these goals. This volume is intended for practitioners who use antidepressants on a daily basis in their practice as well as for the student and researcher. Each will find that it provides a comprehensive and logical approach to this important group of medications. This book is being published as we mark the end of the first 50 years of the modern antidepressant era.

With recent studies using genetic, epigenetic, and other molecular and neurochemical approaches, a new era has begun in understanding pathophysiology of suicide. Emerging evidence suggests that neurobiological factors are not only critical in providing potential risk factors but also provide a promising approach to develop more effective treatment and prevention strategies. The Neurobiological Basis of Suicide discusses the most recent findings in suicide neurobiology. Psychological, psychosocial, and cultural factors are important in determining the risk factors for suicide; however, they offer weak prediction and can be of little clinical use. Interestingly, cognitive characteristics are different among depressed suicidal and depressed nonsuicidal subjects, and could be involved in the development of suicidal behavior. The characterization of the neurobiological basis of suicide is in delineating the risk factors associated with suicide. The Neurobiological Basis of Suicide focuses on how and why these neurobiological factors are crucial in the pathogenic mechanisms of suicidal behavior and how these findings can be transformed into potential therapeutic applications.

Serotonin (5-hydroxytryptamine, often cited as 5-HT) is one of the major excitatory neurotransmitter, and the serotonergic system is one of the best studied and understood transmitter systems. It is crucially involved in the organization of virtually all behaviours and in the regulation of emotion and mood. Alterations in the serotonergic system, induced by e.g. learning or pathological processes, underlie behavioural plasticity and changes in mood, which can finally results in abnormal behaviour and psychiatric conditions. Not surprisingly, the serotonergic system and its functional components appear to be targets for a multitude of pharmacological treatments - examples of very successful drugs targeting the serotoninergic system include Prozac and Zoloft. The last decades of research have not only fundamentally expanded our view on serotonin but also revealed in much more detail an astonishing complexity of this system, which comprises a multitude of receptors and signalling pathways. A detailed view on its role in basal, but also complex, behaviours emerged, and, was presented in a number of single review articles. Although much is known now, the serotonergic system is still a fast growing field of research contributing to our present understanding of the brains function during normal and disturbed behaviour. This handbook aims towards a detailed and comprehensive overview over the many facets of behavioural serotonin research. As such, it will provide the most up to date and thorough reading concerning the serotonergic systems control of behaviour and mood in animals and humans. The goal is to create a systematic overview and first hand reference that can be used by students and scholars alike in the fields of genetics, anatomy, pharmacology, physiology, behavioural neuroscience, pathology, and psychiatry. The chapters in this book will be written by leading scientists in this field. Most of them have already written excellent reviews in their field of expertise. The book is divided in 4 sections. After an historical introduction, illustrating the growth of ideas about serotonin function in behaviour of the last forty years, section A will focus on the functional anatomy of the serotonergic system. Section B provides a review of the neurophysiology of the serotonergic system and its single components. In section C the involvement of serotonin in behavioural organization will be discussed in great detail, while section D deals with the role of serotonin in behavioural pathologies and psychiatric disorders. The first handbook broadly discussing the behavioral neurobiology of the serotonorgic transmitter system Co-edited by one of the pioneers and opinion leaders of the past decades, Barry Jacobs (Princeton), with an international list (10 countries) of highly regarded contributors providing over 50 chapters, and including the leaders in the field in number of articles and citations: K. P. Lesch, T. Sharp, A. Caspi, P. Blier, G.K. Aghajanian, E. C. Azmitia, and others The only integrated and complete resource on the market containing the best information integrating international research, providing a global perspective to an international community Of great value not only for researchers and experts, but also for students and clinicians as a background reference