Research in the opioid field continues apace, with ongoing developments in our understanding of the underlying biology through to the clinical consequences of modulating opioid receptors. The sheer volume of research being carried out in this field precludes a thorough bench-to-bedside review and has necessitated a somewhat focused approach within this volume, in particular the use and potential uses of ligands that activate one, or more, of the receptors. Contributions to Research and Development of Opioid-Related Ligands include chapters describing current research into the main clinical uses of opioids, analgesia and opioid abuse treatment, as well as what the editors consider to be key areas of pre-clinical development. Not surprisingly the identification of a fourth opioid-like receptor, the NOP receptor, has provided the stimulus for many studies with the aim of determining the potential therapeutic value of modulating the activity of this receptor. A number of chapters within this volume reflect the current interest in this new member of the family.
The 16 chapters of Research and Development of Opioid-Related Ligands are arranged into 5 themes, starting with the clinical studies of pain and opioid abuse treatment and followed by chapters on new ligand development, novel assays and concepts, classical opioid pharmacology and NOP receptor pharmacology. An emphasis is placed on translational science and how our increased knowledge may lead to new medicines. The development and use of ligands selective for one receptor or another continues to be of substantial interest, and indeed, the availability of such ligands has allowed the pharmacology of the NOP receptor to be studied in detail from soon after its discovery. Interestingly, ligands induce distinct receptor conformations and produce different signaling cascades, indicating that ligand-directed signaling or biased agonism may have important therapeutic implications. In addition we have now reached a point where selectively promiscuous ligands (ligands that bind to more than one receptor but with defined efficacy at each) can be designed. The rationale for, and progress in, targeting such ligands is made in a number of the chapters.
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Mei-Chuan Ko is affiliated with the Department of Physiology and Pharmacology at Wake Forest University School of Medicine. Stephen M. Husbands is affiliated with the Department of Pharmacy and Pharmacology at the University of Bath.
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