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dc.contributor.authorMoutal, Aubin
dc.contributor.authorShan, Zhiming
dc.contributor.authorMiranda, Victor G
dc.contributor.authorFrançois-Moutal, Liberty
dc.contributor.authorMadura, Cynthia L
dc.contributor.authorKhanna, May
dc.contributor.authorKhanna, Rajesh
dc.date.accessioned2019-12-06T02:54:24Z
dc.date.available2019-12-06T02:54:24Z
dc.date.issued2019-11-02
dc.identifier.citationAubin Moutal, Zhiming Shan, Victor G. Miranda, Liberty François-Moutal, Cynthia L. Madura, May Khanna & Rajesh Khanna (2019) Evaluation of edonerpic maleate as a CRMP2 inhibitor for pain relief, Channels, 13:1, 498-504, DOI: 10.1080/19336950.2019.1684608en_US
dc.identifier.issn1933-6950
dc.identifier.pmid31680630
dc.identifier.doi10.1080/19336950.2019.1684608
dc.identifier.urihttp://hdl.handle.net/10150/636296
dc.description.abstractWe have previously reported that the microtubule-associated collapsin response mediator protein 2 (CRMP2) is necessary for the expression of chronic pain. CRMP2 achieves this control of nociceptive signaling by virtue of its ability to regulate voltage-gated calcium and sodium channels. To date, however, no drugs exist that target CRMP2. Recently, the small molecule edonerpic maleate (1 -{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate), a candidate therapeutic for Alzheimer’s disease was reported to be a novel CRMP2 binding compound with the potential to decrease its phosphorylation level in cortical tissues in vivo. Here we sought to determine the mechanism of action of edonerpic maleate and test its possible effect in a rodent model of chronic pain. We observed: (i) no binding between human CRMP2 and edonerpic maleate; (ii) edonerpic maleate had no effect on CRMP2 expression and phosphorylation in dorsal root ganglion (DRG) neurons; (iii) edonerpic maleate-decreased calcium but increased sodium current density in DRG neurons; and (iv) edonerpic maleate was ineffective in reversing post-surgical allodynia in male and female mice. Thus, while CRMP2 inhibiting compounds remain a viable strategy for developing new mechanism-based pain inhibitors, edonerpic maleate is an unlikely candidate.en_US
dc.description.sponsorshipNational Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01NS098772, 1R01DA042852, R01AT009716]en_US
dc.language.isoenen_US
dc.publisherTAYLOR & FRANCIS INCen_US
dc.rightsCopyright © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCRMP2en_US
dc.subjectDRG sensory neuronen_US
dc.subjectedonerpic maleateen_US
dc.subjection channelsen_US
dc.subjectpost-surgical painen_US
dc.titleEvaluation of edonerpic maleate as a CRMP2 inhibitor for pain reliefen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Ctr Innovat Brain Scien_US
dc.contributor.departmentUniv Arizona Hlth Sci, Coll Med, Dept Pharmacolen_US
dc.identifier.journalCHANNELSen_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.journaltitleChannels (Austin, Tex.)
refterms.dateFOA2019-12-06T02:54:24Z


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Copyright © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Except where otherwise noted, this item's license is described as Copyright © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).