TY - BOOK ID - 135091477 TI - Opioids and Their Receptors : Present and Emerging Concepts in Opioid Drug Discovery AU - Spetea, Mariana AU - Schmidhammer, Helmut PY - 2020 PB - Basel, Switzerland MDPI - Multidisciplinary Digital Publishing Institute DB - UniCat KW - opioid receptors KW - neurokinin-1 receptor KW - peptide synthesis KW - receptor binding studies KW - functional assay KW - writhing test KW - tolerance KW - Leu-enkephalin KW - beta-arrestin KW - mu opioid receptor KW - delta opioid receptor KW - biased signaling KW - DADLE KW - ischemia KW - plasma stability KW - morphinan KW - BNTX KW - δ opioid receptor antagonist KW - 1H-NMR experiments KW - mechanism elucidation KW - peripheral antinociception KW - 14-methoxycodeine-6-O-sulfate KW - codeine-6-O-sulfate KW - opioid peptides and peptidomimetics KW - DAMGO KW - DALDA KW - [Dmt1]DALDA KW - KGOP01 KW - binding KW - molecular docking KW - structure-activity relationships KW - β2-amino acids KW - β2-Homo-amino acids KW - µ-opioid receptor KW - opioid peptides KW - TAPP KW - racemic synthesis of β2-amino acids KW - peripheral µ-opioid receptors KW - analgesia KW - peripheral analgesic tolerance KW - dysbiosis KW - opioid KW - bifunctional ligands KW - (−)-N-phenethylnorhydromorphone analogs KW - [35S]GTPgammaS assay KW - forskolin-induced cAMP accumulation assays KW - β-arrestin recruitment assays KW - MOR and DOR agonists KW - respiratory depression KW - bias factor KW - molecular modeling & KW - simulation KW - δ opioid receptor KW - NTI derivative KW - sulfonamide KW - inverse agonist KW - neutral antagonist KW - agonist KW - opioids KW - mu receptor KW - opioid side effects KW - biased agonism KW - partial agonism KW - zerumbone KW - chronic constriction injury (CCI) KW - allodynia KW - hyperalgesia KW - potassium channels KW - over-the-counter drugs KW - misuse KW - abuse KW - opioid drugs KW - pharmacology KW - codeine KW - dihydrocodeine KW - loperamide KW - opioid peptide KW - macrocyclic tetrapeptide KW - multifunctional ligands KW - kappa opioid receptor KW - analgesics KW - opioid liabilities KW - μ opioid receptor KW - receptor model KW - biased ligands KW - dependence KW - pain therapy KW - neonatal opioid withdrawal syndrome KW - naltrexone KW - 6β-naltrexol KW - buprenorphine KW - G-protein bias KW - arrestin recruitment KW - respiration KW - mitragynine KW - heteromer KW - internalization KW - primary hippocampal culture KW - lysosomes KW - µ opioid receptor KW - molecular dynamics KW - docking KW - interaction fingerprints KW - biased agonists KW - SR-17018 KW - PZM21 KW - morphine KW - fentanyl KW - diphenethylamines KW - design and synthesis KW - structure–activity relationships KW - partial agonist KW - biased agonist KW - antagonist KW - binding affinity KW - selectivity KW - n/a UR - https://www.unicat.be/uniCat?func=search&query=sysid:135091477 AB - 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. ER -