SP0074 Are all opioids the same?. (12th June 2018)

• Record Type: Journal Article
• Authors: Stein, C.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 20
• Page End: 20
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.7740
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects such as respiratory depression, sedation, addiction, nausea and constipation. Novel strategies to avoid adverse effects include the design of "biassed agonists" and of environment-sensitive ligands. Exploiting pathological (rather than physiological) conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, due to its low pKa, selectively activates peripheral mu-opioid receptors in injured/inflamed tissue, i.e. at the source of pain generation. Unlike conventional opioids, this agonist showed pH-sensitive binding, G-protein subunit dissociation, and cAMP inhibition in vitro. It produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation, constipation or addiction potential. Disclosure of Interest: None declared