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dc.contributor.authorOlson, Keith M
dc.contributor.authorDuron, David I
dc.contributor.authorWomer, Daniel
dc.contributor.authorFell, Ryan
dc.contributor.authorStreicher, John M
dc.date.accessioned2019-07-26T00:16:47Z
dc.date.available2019-07-26T00:16:47Z
dc.date.issued2019-06-06
dc.identifier.citationOlson, K. M., Duron, D. I., Womer, D., Fell, R., & Streicher, J. M. (2019). Comprehensive molecular pharmacology screening reveals potential new receptor interactions for clinically relevant opioids. PloS one, 14(6), e0217371.en_US
dc.identifier.issn1932-6203
dc.identifier.pmid31170174
dc.identifier.doi10.1371/journal.pone.0217371
dc.identifier.urihttp://hdl.handle.net/10150/633528
dc.description.abstractMost clinically used opioids are thought to induce analgesia through activation of the mu opioid receptor (MOR). However, disparities have been observed between the efficacy of opioids in activating the MOR in vitro and in inducing analgesia in vivo. In addition, some clinically used opioids do not produce cross-tolerance with each other, and desensitization produced in vitro does not match tolerance produced in vivo. These disparities suggest that some opioids could be acting through other targets in vivo, but this has not been comprehensively tested. We thus screened 9 clinically relevant opioids (buprenorphine, hydrocodone, hydromorphone, morphine, 0-desmethyl-tramadol, oxycodone, oxymorphone, tapentadol, tramadol) against 9 pain-related receptor targets (MOR, delta opioid receptor [DOR], kappa opioid receptor [KOR], nociceptin receptor [NOP], cannabinoid receptor type 1 [CB1], sigma-1 receptor [al R], and the monoamine transporters [NET/SERT/DAT]) expressed in cells using radioligand binding and functional activity assays. We found several novel interactions, including monoamine transporter activation by buprenorphine and al R binding by hydrocodone and tapentadol. Tail flick anti-nociception experiments with CD-1 mice demonstrated that the monoamine transporter inhibitor duloxetine selectively promoted buprenorphine anti-nociception while producing no effects by itself or in combination with the most MOR-selective drug oxymorphone, providing evidence that these novel interactions could be relevant in vivo. Our findings provide a comprehensive picture of the receptor interaction profiles of clinically relevant opioids, which has not previously been performed. Our findings also suggest novel receptor interactions for future investigation that could explain some of the disparities observed between opioid performance in vitro and in vivo.en_US
dc.description.sponsorshipDepomed, Inc.; University of Arizonaen_US
dc.language.isoenen_US
dc.publisherPUBLIC LIBRARY SCIENCEen_US
dc.rights© 2019 Olson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.titleComprehensive molecular pharmacology screening reveals potential new receptor interactions for clinically relevant opioidsen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Med, Dept Pharmacolen_US
dc.identifier.journalPLOS ONEen_US
dc.description.noteOpen access journalen_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.journaltitlePloS one
refterms.dateFOA2019-07-26T00:16:48Z


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