Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids
Date
2019Journal
Journal of Clinical InvestigationPublisher
American Society for Clinical InvestigationType
Article
Metadata
Show full item recordAbstract
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).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/10713/10704ae974a485f413a2113503eed53cd6c53
10.1172/JCI126912