ArticleBritish journal of pharmacology2010
Activation of µ-opioid receptors and block of Kir3 potassium channels and NMDA receptor conductance by L- and D-methadone in rat locus coeruleus.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Analgesic effect of methadone constant rate infusion is not superior to fentanyl constant rate infusion in dogs after spinal surgery: a prospective, randomized, blinded, clinical trial.Frontiers in veterinary science · 2026Trial
- Opioid Add-On Combination Therapy for Cancer Pain: Pharmacological Rationale, Clinical Evidence, and Future Directions.CNS drugs · 2026Review
- The neural circuits and signalling pathways of opioid use disorder.Nature reviews. Neuroscience · 2025Review
- Subcutaneous methadone is not different than transdermal fentanyl for postoperative analgesia in dogs with thoracolumbar disc disease, a prospective, randomised, blinded clinical study.BMC veterinary research · 2025Article
- Microphysiological system to address the opioid crisis: A novel multi-organ model of acute opioid overdose and recovery.Current research in toxicology · 2025Article
- Punica granatum Seed Essential Oil Suppressed Methadone-Induced Cell Death by Natural Antioxidant Activity.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Article
- Influence of methadone on the anticonvulsant efficacy of valproate sodium gabapentin against maximal electroshock seizure in mice by regulation of brain MDA TNF-α.Frontiers in neurology · 2022Article
- Dendritic spine remodeling and plasticity under general anesthesia.Brain structure & function · 2021Review
- Methadone and Ketamine: Boosting Benefits and Still More to Learn.Anesthesiology · 2021Article
- Magnesium Salt, a Simple Strategy to Improve Methadone Analgesia in Chronic Pain: An Isobolographic Preclinical Study in Neuropathic Mice.Frontiers in pharmacology · 2020Article
- Effect of Sinomenine on the Morphine-Dependence and Related Neural Mechanisms in Mice.Neurochemical research · 2017Article
- Characterization of methadone as a β-arrestin-biased μ-opioid receptor agonist.Molecular pain · 2016Article
- Does PKC activation increase the homologous desensitization of μ opioid receptors?British journal of pharmacology · 2015Article
- Buprenorphine signalling is compromised at the N40D polymorphism of the human μ opioid receptor in vitro.British journal of pharmacology · 2014Article
- Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.Pharmacological reviews · 2013Review
- Identification of functional circuitry between retrosplenial and postrhinal cortices during fear conditioning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Characterization of the antinociceptive effects of the individual isomers of methadone after acute and chronic administrations.Behavioural pharmacology · 2011Article
- [Analgesic therapy of calciphylaxis with levomethadone : a case study].Schmerz (Berlin, Germany) · 2010Article
- Association ofBasic and clinical neuroscienceArticle
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeMethadone activates opioid receptors to increase a potassium conductance mediated by G-protein-coupled, inwardly rectifying, potassium (K(IR) 3) channels. Methadone also blocks K(IR) 3 channels and N-methyl-D-aspartic acid (NMDA) receptors. However, the concentration dependence and stereospecificity of receptor activation and channel blockade by methadone on single neurons has not been characterized. EXPERIMENTAL APPROACH: Intracellular and whole-cell recording were made from locus coeruleus neurons in brain slices and the activation of µ-opioid receptors and blockade of K(IR) 3 and NMDA channels with L- and D-methadone was examined. KEY
resultsThe potency of L-methadone, measured by the amplitude of hyperpolarization was 16.5-fold higher than with D-methadone. A maximum hyperpolarization was caused by both enantiomers (∼30 mV); however, the maximum outward current measured with whole-cell voltage-clamp recording was smaller than the current induced by [Met](5) enkephalin. The K(IR) 3 conductance induced by activation of α(2) -adrenoceptors was decreased with high concentrations of L- and D-methadone (10-30 µM). In addition, methadone blocked the resting inward rectifying conductance (K(IR) ). Both L- and D-methadone blocked the NMDA receptor-dependent current. The block of NMDA receptor-dependent current was voltage-dependent suggesting that methadone acted as a channel blocker. CONCLUSIONS AND IMPLICATIONS: Methadone activated µ-opioid receptors at low concentrations in a stereospecific manner. K(IR) 3 and NMDA receptor channel block was not stereospecific and required substantially higher concentrations. The separation in the concentration range suggests that the activation of µ-opioid receptors rather than the channel blocking properties mediate both the therapeutic and toxic actions of methadone.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.