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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/150155
Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids
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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.
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CAI, Ning-Sheng, et al. Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids. Journal of Clinical Investigation. 2019. Vol. 129, num. 7, pags. 2730-2744. ISSN 0021-9738. [consulted: 15 of August of 2026]. Available at: https://hdl.handle.net/2445/150155