The Kappa Opioid Receptor

This book covers the latest knowledge in structure, signaling, and biochemical pharmacology of KOR as well as preclinical research and clinical applications (including clinical phase studies and approved for human use) of KOR compounds. It is divided up into the three parts: Molecular aspects of KOR, Preclinical research on pharmacology of KOR agonists and antagonists in animals and KOR agonists and antagonists in clinical use and in past and present clinical trials. The chapters "Biosensors monitor ligand-selective effects at kappa opioid receptors" and "The role of dynorphin and the kappa opioid receptor in schizophrenia and major depressive disorder: a translational approach" of this book are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

This book covers the latest knowledge in structure, signaling, and biochemical pharmacology of KOR as well as preclinical research and clinical applications (including clinical phase studies and approved for human use) of KOR compounds. It is divided up into the three parts: Molecular aspects of KOR, Preclinical research on pharmacology of KOR agonists and antagonists in animals and KOR agonists and antagonists in clinical use and in past and present clinical trials. The chapters "Biosensors monitor ligand-selective effects at kappa opioid receptors" and "The role of dynorphin and the kappa opioid receptor in schizophrenia and major depressive disorder: a translational approach" of this book are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

The interest in opioids such as morphine, the prototypical opioid ligand, has been maintained through the years. The identification of endogenous opioids and their receptors (mu, delta, kappa, and nociceptin), molecular cloning, and the elucidation of the crystal structures of opioid receptors represent key milestones in opioid research. The opioid system modulates numerous pharmacological responses, with therapeutic (i.e., analgesia) and detrimental side effects (i.e., addiction). The medical use and misuse of opioids have dramatically increased, leading to the 21st century opioid crisis. This book presents recent developments in opioid drug discovery, specifically in the medicinal chemistry and pharmacology of new ligands targeting the opioid receptors as effective and safe therapeutics for human diseases. Furthermore, it draws a special attention to advancing concepts and strategies in opioid drug discovery to mitigate opioid liabilities. The diversity among the discussed topics is a testimony to the complexity of the opioid system, which results from the expression, regulation, and functional role of ligands and receptors. The array of multidisciplinary research areas illustrates the rapidly developing basic research and translational activities in opioid drug discovery. This book will serve as a useful reference while also stimulating continued research in the chemistry and pharmacology of opioids and their receptors, with the prospect of developing improved therapies for human diseases, but also improving health and quality of life in general.

Discovery and Development of Neuroprotective Agents from Natural Products draws together global research on medicinal agents from natural sources as starting points for the design of neuroprotective drugs. From the prediction of promising leads and identification of active agents to the extraction of complex molecules, the book explores a range of important topics to support the development of safer, more economical therapeutics for these increasingly prevalent diseases. Beginning with an overview of current developments in the field, the book goes on to explore the identification, extraction and phytochemistry of such neuroprotective agents as antioxidants, biophenols and naturally occurring anti-inflammatory steroid analogues. Specific natural sources of bioactive agents are reviewed, and the development of these agents into therapeutics for a number of specific neurological disorders, including Alzheimer’s disease, Parkinson’s disease and ischemic brain stroke, are discussed. Combining the expertise of specialists from around the world, this in the Natural Products Drug Discovery series aims to support and encourage researchers in the investigation of natural sources as starting points for the development of standardized, safe and effective neuroprotective drugs. Features chapters written by active researchers and leading global experts deeply engaged in the research field of natural product chemistry for drug discovery Includes comprehensive coverage of cutting-edge research advances in the design of drugs from natural products targeted at different kinds of neurodegenerative diseases Offers a practical review of identification, isolation and extraction techniques to support medicinal chemists in the lab

Comprehensive and authoritative, Opioid Receptors and Antagonists: From Bench to Clinic offers neuroscientists, pharmacologists and interested clinicians a unique survey of the extensive and diverse research efforts currently employed with opioid antagonists to develop novel innovative drug therapies. Summarizes the present understanding of the chemistry, pharmacology and molecular biology of opioid receptors and their subtypes Highlights differences and similarities between the opioid pharmacology of animals and human Describes current and potential therapeutic areas for opioid antagonists, including substance abuse, alcohol and ingestive behaviors, behavioral disorders and other medical indications, supported by nonclinical and clinical evidence Focuses on the development of exciting and innovative drug delivery approaches that are being used with opioid antagonists for the above medical indications

Advances in itch research have elucidated differences between itch and pain but have also blurred the distinction between them. There is a long debate about how somatic sensations including touch, pain, itch, and temperature sensitivity are encoded by the nervous system. Research suggests that each sensory modality is processed along a fixed, direct-line communication system from the skin to the brain. Itch: Mechanisms and Treatment presents a timely update on all aspects of itch research and the clinical treatment of itch that accompanies many dermatological conditions including psoriasis, neuropathic itch, cutaneous t-cells lymphomas, and systemic diseases such as kidney and liver disease and cancer. Composed of contributions from distinguished researchers around the world, the book explores topics such as: Neuropathic itch Peripheral neuronal mechanism of itch The role of PAR-2 in neuroimmune communication and itch Mrgprs as itch receptors The role of interleukin-31 and oncostatin M in itch and neuroimmune communication Spinal coding of itch and pain Spinal microcircuits and the regulation of itch Examining new findings on cellular and molecular mechanisms, the book is a compendium of the most current research on itch, its prevalence in society, and the problems associated with treatment.

The Essence of Analgesia and Analgesics is an invaluable practical resource for clinicians giving pain relief in any clinical setting, describing the pharmacologic principles and clinical use of all available pain medications. As well as detailed overviews of pain processing and analgesic theory, sections are dedicated to oral and panteral opioid analgesics, neuraxial opioids, NSAIDs, local anesthetics, anticonvulsant type analgesics, NMDA antagonists, alpha adrenergic analgesics, antidepressant analgesics, muscle relaxants, adjuvant medications, and new and emerging analgesics. The concise format of the chapters allows for quick and easy reading and assimilation of information. Enhanced by summary tables and figures, each chapter provides an overview of a particular drug, covering chemical structure, mode of activity, indications, contraindications, common doses and uses, advantages and disadvantages, and drug related adverse events. Key references are also provided. Edited by leading experts in pain management, this is essential reading for any clinician involved in pain management.

In 1957 Otto SCHAUMANN, one of the pionieers in pharmacological research on morphine and the first to prepare synthetic opiates, presented a mono graph entitled "Morphin und morphiniihnliche Verbindungen" as Volume 12 of the Handbook of Experimental Pharmacology. Now, 35 years later, we are publishing in the same series a new comprehensive volume covering the present status of opioid research. Since that time the topic has expanded enormously. The identification of opioid receptors and the detection of their endogenous ligands were landmarks which opened a new era in opioid research and fertilized the entire field of neurobiology. The rapid develop ment of this field is illustrated in the figure, which represents the number of papers published on opioid research since 1970 (searches performed on the MEDLINE data base). 3000 Vl.

Basic research on the pharmacology of itch has exploded in the wake of two very influential papers that were published in Nature (2007) and Science (2009). Long overlooked as a milder form of pain, itching has rapidly gained a new appreciation in both research and clinical communities because of its complexity and its negative effects on the quality of life of the distressed patients. Like pain, not all itches are the same. Unlike pain, there are no standard drugs equivalent to aspirin and morphine. Epidemiological studies emphasize the high incidence and economic costs of itch (pruritus). It is the most prevalent symptom of a wide variety of allergic and inflammatory skin conditions (e.g., psoriasis, atopic dermatitis), is associated with several systemic diseases (e.g., chronic kidney and liver disease), and occurs in patients undergoing hemodialysis, spinal administration of opioids, and in those suffering from AIDS. The reader will learn about the multiple pathways for itch and their interactions with pain. The relationship between these closely related, yet distinct sensory phenomena, will be emphasized. Both itch and pain use several common molecules to send signals to the brain. Thus, drugs that have been, and are being, developed as analgesics may also attenuate intractable itch. This has been an exciting and very necessary turn of events since traditional H-1 receptor antagonists are ineffective in blocking the pruritus associated with kidney failure and cholestasis. The clinical chapters will provide insights into contemporary treatment regimens for pruritus in different human scenarios.