ArticleScience translational medicine2018
A bifunctional nociceptin and mu opioid receptor agonist is analgesic without opioid side effects in nonhuman primates.
Article in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 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
79 citing papers in PubMed, 128 citations in OpenAlex.
- Respiratory and Antinociceptive Effects of Nociceptin Receptor-µ-Opioid Receptor Agonist Cebranopadol versus Full Opioid Receptor Agonist Oxycodone: A Comparison in Healthy Volunteers.Anesthesiology · 2026Trial
- Structural factors for receptor binding and activation of the Nociceptin opioid receptor by full and partial agonists.Biochemical pharmacology · 2026Article
- Sex-Specific Relationships Between Nociceptin/Orphanin FQ Peptide (NOP) Receptors and Alcohol Drinking: Longitudinal PET Studies in Cynomolgus Monkeys.Basic & clinical pharmacology & toxicology · 2026Article
- Structural basis for dual targeting of μ-opioid and nociceptin/orphanin FQ receptors by Cebranopadol.Acta pharmacologica Sinica · 2026Article
- Review
- Structural and Pharmacological Characterization of AT-121 Reveals Carbonic Anhydrase Inhibition as a Complementary Mechanism to Dual MOR/NOR Agonism.ACS medicinal chemistry letters · 2026Article
- Synthesis and evaluation of 14β-acyl substituted 17-cyclopropylmethyl-7,8-dihydromorphinone derivatives: mixed partial agonists at mu opioid and nociception/orphanin FQ peptide receptors.RSC medicinal chemistry · 2026Article
- Structure-based design of an opioid receptor modulator for enhanced morphine analgesia.Science advances · 2026Article
- The Therapeutic Potential of Dual NMR (NOP/MOP) Agonism in Pain Management.Pain and therapy · 2026Review
- Design, Synthesis, and Characterization of Novel, Subtype-Selective Fluorescent Antagonists Targeting the Nociceptin/Orphanin FQ Opioid Peptide Receptor.Journal of medicinal chemistry · 2026Article
- Mu-opioid and nociceptin receptors show divergent, cell-type-specific actions in the mesocorticolimbic reward system in opioid use disorder.Frontiers in cellular neuroscience · 2026Review
- Evaluation of AT121 versus morphine on cortical neurons electrophysiology and dopamine concentrations in hippocampal cells.PloS one · 2026Article
- Buprenorphine Pharmacodynamics: A Bridge to Understanding Buprenorphine Clinical Benefits.Drugs · 2025Review
- Recommended Opioid Receptor Tool Compounds: ComparativeACS pharmacology & translational science · 2025Article
- NOP agonist AT-403 promoted sleep in lactic acid-induced acute pain model.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- Effect of chronic delivery of the NOP/MOR partial agonist AT-201 and NOP antagonist J-113397 on heroin relapse in a rat model of opioid maintenance.Psychopharmacology · 2024Article
- Opioid system and related ligands: from the past to future perspectives.Journal of anesthesia, analgesia and critical care · 2024Review
- Discovery of ITI-333, a Novel Orally Bioavailable Molecule Targeting Multiple Receptors for the Treatment of Pain and Other Disorders.Journal of medicinal chemistry · 2024Article
- Targeting Nociceptin/Orphanin FQ receptor to rescue cognitive symptoms in a mouse neuroendocrine model of chronic stress.Molecular psychiatry · 2024Article
- A Balancing Act: Learning from the Past to Build a Future-Focused Opioid Strategy.Annual review of physiology · 2024Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Misuse of prescription opioids, opioid addiction, and overdose underscore the urgent need for developing addiction-free effective medications for treating severe pain. Mu opioid peptide (MOP) receptor agonists provide very effective pain relief. However, severe side effects limit their use in the clinical setting. Agonists of the nociceptin/orphanin FQ peptide (NOP) receptor have been shown to modulate the antinociceptive and reinforcing effects of MOP agonists. We report the discovery and development of a bifunctional NOP/MOP receptor agonist, AT-121, which has partial agonist activity at both NOP and MOP receptors. AT-121 suppressed oxycodone's reinforcing effects and exerted morphine-like analgesic effects in nonhuman primates. AT-121 treatment did not induce side effects commonly associated with opioids, such as respiratory depression, abuse potential, opioid-induced hyperalgesia, and physical dependence. Our results in nonhuman primates suggest that bifunctional NOP/MOP agonists with the appropriate balance of NOP and MOP agonist activity may provide a dual therapeutic action for safe and effective pain relief and treating prescription opioid abuse.
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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.