Show simple item record

dc.contributor.authorOlson, Keith M
dc.contributor.authorLei, Wei
dc.contributor.authorKeresztes, Attila
dc.contributor.authorLaVigne, Justin
dc.contributor.authorStreicher, John M
dc.date.accessioned2018-08-07T17:13:02Z
dc.date.available2018-08-07T17:13:02Z
dc.date.issued2017-03-29
dc.identifier.citationOlson KM, Lei W, Keresztes A, LaVigne J, and Streicher JM. 2017. Novel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain. Yale Journal of Biology and Medicine. 90(1):97-110.en_US
dc.identifier.issn1551-4056
dc.identifier.pmid28356897
dc.identifier.urihttp://hdl.handle.net/10150/628348
dc.description.abstractOpioid drugs like morphine and fentanyl are the gold standard for treating moderate to severe acute and chronic pain. However, opioid drug use can be limited by serious side effects, including constipation, tolerance, respiratory suppression, and addiction. For more than 100 years, we have tried to develop opioids that decrease or eliminate these liabilities, with little success. Recent advances in understanding opioid receptor signal transduction have suggested new possibilities to activate the opioid receptors to cause analgesia, while reducing or eliminating unwanted side effects. These new approaches include designing functionally selective ligands, which activate desired signaling cascades while avoiding signaling cascades that are thought to provoke side effects. It may also be possible to directly modulate downstream signaling through the use of selective activators and inhibitors. Separate from downstream signal transduction, it has also been found that when the opioid system is stimulated, various negative feedback systems are upregulated to compensate, which can drive side effects. This has led to the development of multi-functional molecules that simultaneously activate the opioid receptor while blocking various negative feedback receptor systems including cholecystokinin and neurokinin-1. Other novel approaches include targeting heterodimers of the opioid and other receptor systems which may drive side effects, and making endogenous opioid peptides druggable, which may also reduce opioid mediated side effects. Taken together, these advances in our molecular understanding provide a path forward to break the barrier in producing an opioid with reduced or eliminated side effects, especially addiction, which may provide relief for millions of patients.en_US
dc.language.isoenen_US
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369049/en_US
dc.rightsCopyright © 2017, Yale Journal of Biology and Medicine. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectChronic Painen_US
dc.subjectDrug Discoveryen_US
dc.subjectFunctional Selectivityen_US
dc.subjectNovel Strategiesen_US
dc.subjectNovel Targetsen_US
dc.subjectOpioiden_US
dc.titleNovel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain.en_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Med, Dept Pharmacolen_US
dc.contributor.departmentUniv Arizona, Dept Chem & Biochemen_US
dc.identifier.journalYale Journal of Biology and Medicineen_US
dc.description.noteOpen access journal.en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleThe Yale journal of biology and medicine
refterms.dateFOA2018-08-07T17:13:02Z


Files in this item

Thumbnail
Name:
yjbm_90_1_97.pdf
Size:
861.4Kb
Format:
PDF
Description:
Final Published Version

This item appears in the following Collection(s)

Show simple item record

Copyright © 2017, Yale Journal of Biology and Medicine. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License.
Except where otherwise noted, this item's license is described as Copyright © 2017, Yale Journal of Biology and Medicine. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License.