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    Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids

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    Author
    Cai, N.-S.
    Quiroz, C.
    Bonaventura, J.
    Date
    2019
    Journal
    Journal of Clinical Investigation
    Publisher
    American Society for Clinical Investigation
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1172/JCI126912
    Abstract
    Identifying nonaddictive opioid medications is a high priority in medical science, but μ-opioid receptors (MORs) mediate both the analgesic and addictive effects of opioids. We found a significant pharmacodynamic difference between morphine and methadone that is determined entirely by heteromerization of MORs with galanin Gal1 receptors (Gal1Rs), rendering a profound decrease in the potency of methadone. This finding was explained by the weaker proficiency of methadone in activating the dopaminergic system as compared with morphine and predicted a dissociation of the therapeutic and euphoric effects of methadone, which was corroborated by a significantly lower incidence of self-reports of feeling “high” in methadone-medicated patients. These results suggest that μ-opioid–Gal1R heteromers mediate the dopaminergic effects of opioids. The results further suggest a lower addictive liability of some opioids, such as methadone, due to their selective low potency for the μ-opioid–Gal1R heteromer.
    Sponsors
    This study was supported by intramural funds from the NIDA and by grants from the Restless Legs Foundation; the Foundation for Science of the Therapeutic Experience; the University of Maryland MPowering the State Opioid Use Disorder initiative; the “Ministerio de Economía y Competitividad” with FEDER funds (SAF2017-87629-R); and the “Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas” (CB06/05/0064).
    Keyword
    Methadone
    Morphine
    Receptor, Galanin, Type 1
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063967898&doi=10.1172%2fJCI126912&partnerID=40&md5=464d7311b10f9903ec894294b828672d; http://hdl.handle.net/10713/10704
    ae974a485f413a2113503eed53cd6c53
    10.1172/JCI126912
    Scopus Count
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    UMB Open Access Articles 2019

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