ArticleMolecular pain2016
Characterization of methadone as a β-arrestin-biased μ-opioid receptor agonist.
Article in Molecular pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 27 citations in OpenAlex.
- Effects of two structurally diverse positive allosteric modulators on signaling bias at the μ-opioid receptor.Molecular pharmacology · 2025Article
- Methadone and Buprenorphine as Medication for Addiction Treatment Diversely Affect Inflammation and Craving Depending on Their Doses.Pharmacy (Basel, Switzerland) · 2025Article
- Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms.Therapeutic advances in psychopharmacology · 2025Review
- Enhanced Recovery After Surgery (ERAS) protocols for spine surgery - review of literature.Anaesthesiology intensive therapy · 2022Review
- Time-Dependent Changes in the Serum Levels of Neurobiochemical Factors After Acute Methadone Overdose in Adolescent Male Rat.Cellular and molecular neurobiology · 2021Article
- Atomic-Level Characterization of the Methadone-Stabilized Active Conformation ofMolecular pharmacology · 2020Article
- Retrospective analysis reveals significant association of hypoglycemia with tramadol and methadone in contrast to other opioids.Scientific reports · 2019Article
- Do All Opioid Drugs Share the Same Immunomodulatory Properties? A Review From Animal and Human Studies.Frontiers in immunology · 2019Review
- Efficacy of D,L-methadone in the treatment of glioblastoma in vitro.CNS oncology · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMethadone is a unique µ-opioid receptor agonist. Although several researchers have insisted that the pharmacological effects of methadone are mediated through the blockade of NMDA receptor, the underlying mechanism by which methadone exerts its distinct pharmacological effects compared to those of other µ-opioid receptor agonists is still controversial. In the present study, we further investigated the pharmacological profile of methadone compared to those of fentanyl and morphine as measured mainly by the discriminative stimulus effect and in vitro assays for NMDA receptor binding, µ-opioid receptor-internalization, and µ-opioid receptor-mediated β-arrestin recruitment.
resultsWe found that fentanyl substituted for the discriminative stimulus effects of methadone, whereas a relatively high dose of morphine was required to substitute for the discriminative stimulus effects of methadone in rats. Under these conditions, the non-competitive NMDA receptor antagonist MK-801 did not substitute for the discriminative stimulus effects of methadone. In association with its discriminative stimulus effect, methadone failed to displace the receptor binding of MK801 using mouse brain membrane. Methadone and fentanyl, but not morphine, induced potent µ-opioid receptor internalization accompanied by the strong recruitment of β-arrestin-2 in µ-opioid receptor-overexpressing cells.
conclusionsThese results suggest that methadone may, at least partly, produce its pharmacological effect as a β-arrestin-biased µ-opioid receptor agonist, similar to fentanyl, and NMDA receptor blockade is not the main contributor to the pharmacological profile of methadone.
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