06569nam 2201753z- 450 991055710800332120231214132947.0(CKB)5400000000040967(oapen)https://directory.doabooks.org/handle/20.500.12854/69428(EXLCZ)99540000000004096720202105d2020 |y 0engurmn|---annantxtrdacontentcrdamediacrrdacarrierOpioids and Their ReceptorsPresent and Emerging Concepts in Opioid Drug DiscoveryBasel, SwitzerlandMDPI - Multidisciplinary Digital Publishing Institute20201 electronic resource (358 p.)3-0365-0046-4 3-0365-0047-2 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.Opioids and Their Receptors Medicinebicsscopioid receptorsneurokinin-1 receptorpeptide synthesisreceptor binding studiesfunctional assaywrithing testtoleranceLeu-enkephalinbeta-arrestinmu opioid receptordelta opioid receptorbiased signalingDADLEischemiaplasma stabilitymorphinanBNTXδ opioid receptor antagonist1H-NMR experimentsmechanism elucidationperipheral antinociception14-methoxycodeine-6-O-sulfatecodeine-6-O-sulfateopioid peptides and peptidomimeticsDAMGODALDA[Dmt1]DALDAKGOP01bindingmolecular dockingstructure-activity relationshipsβ2-amino acidsβ2-Homo-amino acidsµ-opioid receptoropioid peptidesTAPPracemic synthesis of β2-amino acidsperipheral µ-opioid receptorsanalgesiaperipheral analgesic tolerancedysbiosisopioidbifunctional ligands(−)-N-phenethylnorhydromorphone analogs[35S]GTPgammaS assayforskolin-induced cAMP accumulation assaysβ-arrestin recruitment assaysMOR and DOR agonistsrespiratory depressionbias factormolecular modeling &ampsimulationδ opioid receptorNTI derivativesulfonamideinverse agonistneutral antagonistagonistopioidsmu receptoropioid side effectsbiased agonismpartial agonismzerumbonechronic constriction injury (CCI)allodyniahyperalgesiapotassium channelsover-the-counter drugsmisuseabuseopioid drugspharmacologycodeinedihydrocodeineloperamideopioid peptidemacrocyclic tetrapeptidemultifunctional ligandskappa opioid receptoranalgesicsopioid liabilitiesμ opioid receptorreceptor modelbiased ligandsdependencepain therapyneonatal opioid withdrawal syndromenaltrexone6β-naltrexolbuprenorphineG-protein biasarrestin recruitmentrespirationmitragynineheteromerinternalizationprimary hippocampal culturelysosomesµ opioid receptormolecular dynamicsdockinginteraction fingerprintsbiased agonistsSR-17018PZM21morphinefentanyldiphenethylaminesdesign and synthesisstructure-activity relationshipspartial agonistbiased agonistantagonistbinding affinityselectivityMedicineSpetea Marianaedt1304705Schmidhammer HelmutedtSpetea MarianaothSchmidhammer HelmutothBOOK9910557108003321Opioids and Their Receptors3027635UNINA