Main description:

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.

Contents:

Preface ; Commentaries ; 1. Commentary on the Current Status of Clinically Used Analgesics ; Thomas M. Dodds ; 2. Commentary on the Current State of Opioid-Related Research ; John W. Lewis ; Clinical Studies of Pain and Opioids ; 3. The Clinical Importance of Conditioning Pain Modulation: A Review and ; Clinical Implications ; Mellar P. Davis ; 4. Treatment of Pain and Opioid Abuse ; Shanthi Mogali and Sandra D. Comer ; 5. Treatment of Opioid Dependence ; Andrew J. Saxon ; 6. Buprenorphine in the Treatment of Neuropathic Pain ; Guy H. Hans ; Development of New Ligands ; 7. Buprenorphine and Related Orvinols ; Stephen M. Husbands ; 8. Structure-Activity Relationships of Nociceptin Receptor (NOP) Ligands ; and the Design of Bifunctional NOP/Mu Opioid Receptor-Targeted ; Ligands ; Nurulain T. Zaveri, Dennis Yasuda, Blair V. Journigan, Pankaj R. Daga, ; Faming Jiang, and Cris Olsen ; Novel Assays and Concepts ; 9. Mu, Delta and Kappa Opioid Agonist Effects In Novel Assays of ; Pain-Depressed Behavior ; S. Stevens Negus and Ahmad A. Altarifi ; 10. Functionally Biased Agonism of Mu and Kappa Opioid Receptors ; Donald J. Kyle ; Pharmacology of Classical Opioid Receptors ; 11. Peripherally Restricted Opioid Analgesics ; Patrick J. Little ; 12. The Delta Opioid Receptor ; A. M. Symons-Liguori and T. W. Vanderah ; 13. Kappa Opioids: Problems and Opportunities in Analgesia ; Eduardo R. Butelman and Mary Jeanne Kreek ; 14. Mixed Mu/Kappa Opioid Agonists ; Jean M. Bidlack and Brian I. Knapp ; Pharmacology of NOP Receptors ; 15. Medicinal Chemistry, Pharmacology, and Biological Actions of Peptide ; Ligands Selective for the Nociceptin/Orphanin FQ Receptor ; Girolamo Calo' and Remo Guerrini ; 16. A Review of the NOP (ORL-1)-Nociceptin/Orphanin FQ System Covering ; Receptor Structure, Distribution, Role in Analgesia and Reward and ; Interactions with Other Receptors ; Garth T. Whiteside and Donald J. Kyle ; 17. Pharmacology of Mixed NOP/Mu Ligands ; Lawrence Toll, Taline V. Khroyan, Willma E. Polgar, Stephen M. Husbands, and ; Nurulain T. Zaveri ; 18. Pharmacological Investigation of NOP-Related Ligands as Analgesics ; without Abuse Liability ; Devki Sukhtankar and Mei-Chuan Ko ; Editors' Biographies ; Indexes ; Author Index ; Subject Index