ArticleThe Journal of pharmacology and experimental therapeutics2009
The relative potency of inverse opioid agonists and a neutral opioid antagonist in precipitated withdrawal and antagonism of analgesia and toxicity.
Article in The Journal of pharmacology and experimental therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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
22 citing papers in PubMed, 50 citations in OpenAlex.
- Trial
- Reserpine-induced fibromyalgia model in female rats is a long-lasting painful condition masked by antinociceptive endogenous opioids.Frontiers in pharmacology · 2026Article
- In vitro and in vivo pharmacological characterization of fentanyl analogs.Neuropharmacology · 2025Article
- Fentanyl overdose: Temporal effects and prognostic factors in SKH1 mice.Basic & clinical pharmacology & toxicology · 2024Article
- Ligand-Free Signaling of G-Protein-Coupled Receptors: Physiology, Pharmacology, and Genetics.Molecules (Basel, Switzerland) · 2023Review
- Ligand-Free Signaling of G-Protein-Coupled Receptors: Relevance to μ Opioid Receptors in Analgesia and Addiction.Molecules (Basel, Switzerland) · 2022Review
- Postsurgical Latent Pain Sensitization Is Driven by Descending Serotonergic Facilitation and Masked by µ-Opioid Receptor Constitutive Activity in the Rostral Ventromedial Medulla.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- The Potential of Methocinnamox as a Future Treatment for Opioid Use Disorder: A Narrative Review.Pharmacy (Basel, Switzerland) · 2022Review
- Cellular Tolerance Induced by Chronic Opioids in the Central Nervous System.Frontiers in systems neuroscience · 2022Review
- Biased Opioid Antagonists as Modulators of Opioid Dependence: Opportunities to Improve Pain Therapy and Opioid Use Management.Molecules (Basel, Switzerland) · 2020Review
- Lack of Antinociceptive Cross-Tolerance With Co-Administration of Morphine and Fentanyl Into the Periaqueductal Gray of Male Sprague-Dawley Rats.The journal of pain · 2019Article
- High-dose naloxone, an experimental tool uncovering latent sensitisation: pharmacokinetics in humans.British journal of anaesthesia · 2019Article
- Constitutive Desensitization of Opioid Receptors in Peripheral Sensory Neurons.The Journal of pharmacology and experimental therapeutics · 2016Article
- Preferential Delivery of an Opioid Antagonist to the Fetal Brain in Pregnant Mice.The Journal of pharmacology and experimental therapeutics · 2016Article
- Species differences in the effects of the κ-opioid receptor antagonist zyklophin.Alcohol (Fayetteville, N.Y.) · 2016Article
- Maturational alterations in constitutive activity of medial prefrontal cortex kappa-opioid receptors in Wistar rats.Journal of neurochemistry · 2015Article
- The one-two punch of alcoholism: role of central amygdala dynorphins/kappa-opioid receptors.Biological psychiatry · 2014Article
- Constitutive μ-opioid receptor activity leads to long-term endogenous analgesia and dependence.Science (New York, N.Y.) · 2013Article
- Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat.The journal of pain · 2012Article
- The role of opioid antagonist efficacy and constitutive opioid receptor activity in the opioid withdrawal syndrome in mice.Pharmacology, biochemistry, and behavior · 2011Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Opioid antagonists can be classified as inverse agonists and neutral antagonists. In the opioid-dependent state, neutral antagonists are significantly less potent in precipitating withdrawal than inverse agonists. Consequently, neutral opioid antagonists may offer advantages over inverse agonists in the management of opioid overdose. In this study, the relative potency of three opioid antagonists to block opioid analgesia and toxicity and precipitate withdrawal was examined. First, the potency of two opioid inverse agonists (naltrexone and naloxone) and a neutral antagonist (6beta-naltrexol) to antagonize fentanyl-induced analgesia and lethality was determined. The order of potency to block analgesia was naltrexone > naloxone > 6beta-naltrexol (17, 4, 1), which was similar to that to block lethality (13, 2, 1). Next, the antagonists were compared using withdrawal jumping in fentanyl-dependent mice. The order of potency to precipitate withdrawal jumping was naltrexone > naloxone 6beta-naltrexol (1107, 415, 1). The relative potencies to precipitate withdrawal for the inverse agonists compared with the neutral antagonist were dramatically different from that for antagonism of analgesia and lethality. Finally, the effect of 6beta-naltrexol pretreatment on naloxone-precipitated jumping was determined in morphine and fentanyl-dependent mice. 6beta-Naltrexol pretreatment decreased naloxone precipitated withdrawal, indicating that 6beta-naltrexol is a neutral antagonist. These data demonstrate that inverse agonists and neutral antagonists have generally comparable potencies to block opioid analgesia and lethality, whereas the neutral opioid antagonist is substantially less potent in precipitating opioid withdrawal. These results support suggestions that neutral antagonists may have advantages over inverse agonists in the management of opioid overdose.
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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.