Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/150155
Title: | Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids |
Author: | Cai, Ning-Sheng Quiroz, César Bonaventura, Jordi Bonifazi, Alessandro Cole, Thomas O. Purks, Julia Billing, Amy S. Massey, Ebonie Wagner, Michael Wish, Eric D. Guitart, Xavier Rea, William Lam, Sherry Moreno Guillén, Estefanía Casadó Anguera, Verònica Greenblatt, Aaron D. Jacobson, Arthur E. Rice, Kenner C. Casadó, Vicent Newman, Amy Hauck Winkelman, John W. Michaelides, Michael Weintraub, Eric Volkow, Nora D., 1956- Belcher, Annabelle M. Ferré, Sergi |
Keywords: | Receptors neurals Dopamina Neural receptor Dopamine |
Issue Date: | 26-Mar-2019 |
Publisher: | American Society for Clinical Investigation |
Abstract: | Identifying non-addictive opioid medications is a high priority in medical sciences, but μ-opioid receptors 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 μ-opioid receptors with galanin Gal1 receptors, rendering a profound decrease in the potency of methadone. This was explained by methadone's weaker proficiency to activate the dopaminergic system as compared to morphine and predicted a dissociation of therapeutic versus euphoric effects of methadone, which was corroborated by a significantly lower incidence of self-report of 'high' in methadone-maintained patients. These results suggest that μ-opioid-Gal1 receptor heteromers mediate the dopaminergic effects of opioids that may lead to a lower addictive liability of opioids with selective low potency for the μ-opioid-Gal1 receptor heteromer, exemplified by methadone. |
Note: | Reproducció del document publicat a: https://doi.org/10.1172/JCI126912 |
It is part of: | Journal of Clinical Investigation, 2019, vol. 129, num. 7, p. 2730-2744 |
URI: | http://hdl.handle.net/2445/150155 |
Related resource: | https://doi.org/10.1172/JCI126912 |
ISSN: | 0021-9738 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
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