Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids.

ABSTRACT: Identifying non-addictive opioid medications is a high priority in medical sciences, but ?-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 ?-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 ?-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 ?-opioid-Gal1 receptor heteromer, exemplified by methadone.

SUBMITTER: Cai NS 

PROVIDER: S-EPMC6597217 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature