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Papers of the Week

Papers: 13 Apr 2019 - 19 Apr 2019

Animal Studies, Pharmacology/Drug Development

2019 Mar 26

J Clin Invest


Editor's Pick

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


Cai N-S, Quiroz C, Bonaventura J, Bonifazi A, Cole TO, Purks J, Billing AS, Massey E, Wagner M, Wish ED, Guitart X, Rea W, Lam S, Moreno E, Casadó-Anguera V, Greenblatt AD, Jacobson AE, Rice KC, Casadó V, Newman AH, et al.
J Clin Invest. 2019 Mar 26; 130.
PMID: 30913037.


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.