title: G-Protein-Coupled Receptors: Sustained Signaling via Intracellular Megaplexes and Pathway-Specific Drugs.
abstract: Together forever? Functional selection was applied to finally achieve separation of the analgesic properties of opiods from serious side effects such as potentially lethal respiratory depression. A Gi-biased μ-opioid-receptor agonist (PZM21) was identified that stabilizes previously unexplored receptor conformations. This compound relieves pain in mice without causing hypoventilation or addiction.
authors: Institut für Pharmazie, Ernst-Moritz-Arndt-Universität Greifswald, 17487, Greifswald, Germany.
authors: Andreas
authors: 0000-0003-1262-6636
authors: A
authors: Link
authors: Pharmazeutisches Institut und Pharma-Zentrum Bonn, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
authors: Christa E
authors: CE
authors: Müller
mesh_terms: D000701:Analgesics, Opioid / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D043562:Receptors, G-Protein-Coupled
keywords: GPCRs; drug design; medicinal chemistry; receptors; signal transduction