ArticlePloS one2008
High-affinity naloxone binding to filamin a prevents mu opioid receptor-Gs coupling underlying opioid tolerance and dependence.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Low-Dose Naltrexone for Chronic Pain: Update and Systemic Review.Current pain and headache reports · 2020Pooled it
- Ultralow Dose of Naloxone as an Adjuvant to Intrathecal Morphine Infusion Improves Perceived Quality of Sleep but Fails to Alter Persistent Pain: A Randomized, Double-blind, Controlled Study.The Clinical journal of pain · 2015Trial
- Human abuse liability assessment of oxycodone combined with ultra-low-dose naltrexone.Psychopharmacology · 2010Trial
- Low-Dose Naltrexone: What is the Evidence? A Narrative Review.Advances in therapy · 2026Review
- Pharmacological and Non-pharmacological Approaches for the Management of Neuropathic Pain in Multiple Sclerosis.CNS drugs · 2024Review
- Knowing the Enemy Is Halfway towards Victory: A Scoping Review on Opioid-Induced Hyperalgesia.Journal of clinical medicine · 2022Article
- Opioid-Induced Pronociceptive Signaling in the Gastrointestinal Tract Is Mediated by Delta-Opioid Receptor Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
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- Substance abuse and neurotransmission.Advances in pharmacology (San Diego, Calif.) · 2022Article
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- Reconsidering the Usefulness of Adding Naloxone to Buprenorphine.Frontiers in psychiatry · 2020Article
- Mining the NaBiochemical pharmacology · 2019Review
- Genetic neuromuscular disorders: living the era of a therapeutic revolution. Part 1: peripheral neuropathies.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019Review
- Naltrexone treatment reverses astrocyte atrophy and immune dysfunction in self-harming macaques.Brain, behavior, and immunity · 2015Article
- Challenges for opioid receptor nomenclature: IUPHAR Review 9.British journal of pharmacology · 2015Review
- Polytherapy with a combination of three repurposed drugs (PXT3003) down-regulates Pmp22 over-expression and improves myelination, axonal and functional parameters in models of CMT1A neuropathy.Orphanet journal of rare diseases · 2014Article
- Glial TLR4 signaling does not contribute to opioid-induced depression of respiration.Journal of applied physiology (Bethesda, Md. : 1985) · 2014Article
Corrections and comments
- Retraction · 2022-03-30Concerns/Issues about Data · Concerns/Issues about Image · Duplication of/in Image · · see also: https://pubpeer.com/publications/0B03A2B682AAAD6A8E9D7C2C49DD22
- Retracted
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ultra-low-dose opioid antagonists enhance opioid analgesia and reduce analgesic tolerance and dependence by preventing a G protein coupling switch (Gi/o to Gs) by the mu opioid receptor (MOR), although the binding site of such ultra-low-dose opioid antagonists was previously unknown. Here we show that with approximately 200-fold higher affinity than for the mu opioid receptor, naloxone binds a pentapeptide segment of the scaffolding protein filamin A, known to interact with the mu opioid receptor, to disrupt its chronic opioid-induced Gs coupling. Naloxone binding to filamin A is demonstrated by the absence of [(3)H]-and FITC-naloxone binding in the melanoma M2 cell line that does not contain filamin or MOR, contrasting with strong [(3)H]naloxone binding to its filamin A-transfected subclone A7 or to immunopurified filamin A. Naloxone binding to A7 cells was displaced by naltrexone but not by morphine, indicating a target distinct from opioid receptors and perhaps unique to naloxone and its analogs. The intracellular location of this binding site was confirmed by FITC-NLX binding in intact A7 cells. Overlapping peptide fragments from c-terminal filamin A revealed filamin A(2561-2565) as the binding site, and an alanine scan of this pentapeptide revealed an essential mid-point lysine. Finally, in organotypic striatal slice cultures, peptide fragments containing filamin A(2561-2565) abolished the prevention by 10 pM naloxone of both the chronic morphine-induced mu opioid receptor-Gs coupling and the downstream cAMP excitatory signal. These results establish filamin A as the target for ultra-low-dose opioid antagonists previously shown to enhance opioid analgesia and to prevent opioid tolerance and dependence.
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What OpenQuestion holds
Registered trials
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.