title: Biased mu-opioid receptor ligands: a promising new generation of pain therapeutics.
abstract: Opioid chemistry and biology occupy a pivotal place in the history of pharmacology and medicine. Morphine offers unmatched efficacy in alleviating acute pain, but is also associated with a host of adverse side effects. The advent of biased agonism at G protein-coupled receptors has expanded our understanding of intracellular signaling and highlighted the concept that certain ligands are able to differentially modulate downstream pathways. The ability to target one pathway over another has allowed for the development of biased ligands with robust clinical efficacy and fewer adverse events. In this review we summarize these concepts with an emphasis on biased mu opioid receptor pharmacology and highlight how far opioid pharmacology has evolved.
authors.affiliation: Trevena Inc., 1018 West 8th Avenue, Suite A, King of Prussia, PA 19406, USA.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Siuda
authors.affiliation: Trevena Inc., 1018 West 8th Avenue, Suite A, King of Prussia, PA 19406, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Carr
authors.affiliation: Trevena Inc., 1018 West 8th Avenue, Suite A, King of Prussia, PA 19406, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Rominger
authors.affiliation: Trevena Inc., 1018 West 8th Avenue, Suite A, King of Prussia, PA 19406, USA. Electronic address: JViolin@trevena.com.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Violin
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D015195:Drug Design; D006801:Humans; D008024:Ligands; D009020:Morphine / Q000009:adverse effects / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D008024:Ligands; D017450:Receptors, Opioid, mu; D009020:Morphine