Addressing the Interactions between Opioid Ligands and Their Receptors Classic and Nonclassic Cases

CONTENTS 13.1 Introduction 230 13.2 Structure and Functions of the Opioid Receptors 230 13.3 Opioid Ligands 232 13.3.1 MOR Agonists Derived from Morphine and Fentanyl 232 13.3.2 DOR and KOR Agonists 232 13.3.3 Endogenous Opioid Peptides 233 13.3.4 Nonopioid Peptides 234 13.3.5 Peptidomimetics 234 13.4 Opioid Ligand–Receptor Interaction Models 236 13.4.1 Investigation of the Interactions between Opioid Ligands and Receptors 236 13.4.2 Morphine 236 13.4.3 Fentanyls 236 13.4.4 MOR-Selective Peptide and Peptidomimetic Agonists 237 13.4.5 DOR Agonists238 13.4.6 KOR Agonists 238 13.5 Opioid Ligands Deprived of Some Pharmacophores 239 13.5.1 Derivatization or Deletion of Tyr1 239 13.5.2 The Case of Salvinorin 241 13.5.3 The Case of Cycloendomorphins 242 13.6 Conclusions 246 Acknowledgments 246 References 246