ArticlePsychopharmacology2017
Effects of nalfurafine on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone: modeling an abuse-deterrent opioid analgesic in rats.
Article in Psychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- A review of the kappa opioid receptor system in opioid use.Neuroscience and biobehavioral reviews · 2024Pooled it
- Triazole 187 is a biased KOR agonist that suppresses itch without sedation and induces anxiolytic-like behaviors in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Effects of repeated nalfurafine and VZTK35 treatments on fentanyl/cocaine mixture self-administration in a rat drug-vs.-food choice procedure.Psychopharmacology · 2026Article
- Review
- KOR agonists for the treatment and/or prevention of opioid use disorder and cocaine use disorder.Pharmacology, biochemistry, and behavior · 2025Review
- Nalfurafine reverses fentanyl-induced muscle rigidity and respiratory depression without affecting sedation in rats: decoupling respiration from sedation.Journal of applied physiology (Bethesda, Md. : 1985) · 2025Article
- Deletion of β-arrestin 2 in mice affects kappa opioid receptor-mediated behaviors depending on sex, ovariectomy status, and behavioral endpoints.Neuroscience letters · 2025Article
- Comparison of the reinforcing, antinociceptive, and respiratory depressant effects of prototypical and G-protein biased mu-opioid receptor agonists in male and female Sprague-Dawley rats.Psychopharmacology · 2024Article
- Suvorexant enhances oxycodone-induced respiratory depression in male rats.Drug and alcohol dependence · 2024Article
- Assessment of the antinociceptive, respiratory-depressant, and reinforcing effects of the low pKNeuropharmacology · 2024Article
- Systematic Structure-Activity Relationship Study of Nalfurafine Analogues toward Development of Potentially Nonaddictive Pain Management Treatments.Journal of medicinal chemistry · 2024Article
- Contingent administration of typical and biased kappa opioid agonists reduces cocaine and oxycodone choice in a drug vs. food choice procedure in male rhesus monkeys.Psychopharmacology · 2024Article
- Oxycodone: A Current Perspective on Its Pharmacology, Abuse, and Pharmacotherapeutic Developments.Pharmacological reviews · 2023Review
- Quantification of observable behaviors following oral administration of oxycodone and nalfurafine in male rhesus monkeys.Drug and alcohol dependence · 2023Article
- Characterization of a Potential KOR/DOR Dual Agonist with No Apparent Abuse Liability via a Complementary Structure-Activity Relationship Study on Nalfurafine Analogues.ACS chemical neuroscience · 2022Article
- Differential Effects of Cannabidiol and a Novel Cannabidiol Analog on Oxycodone Place Preference and Analgesia in Mice: an Opioid Abuse Deterrent with Analgesic Properties.Cannabis and cannabinoid research · 2022Article
- Evaluation of the Intracellular Signaling Activities of κ-Opioid Receptor Agonists, Nalfurafine Analogs; Focusing on the Selectivity of G-Protein- and β-Arrestin-Mediated Pathways.Molecules (Basel, Switzerland) · 2022Article
- Application of dose-addition analyses to characterize the abuse-related effects of drug mixtures.Journal of the experimental analysis of behavior · 2022Review
- Signaling underlying kappa opioid receptor-mediated behaviors in rodents.Frontiers in neuroscience · 2022Review
- Preclinical Studies on Nalfurafine (TRK-820), a Clinically Used KOR Agonist.Handbook of experimental pharmacology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
rationaleStrategies to reduce the misuse of mu opioid agonists are critically needed. Previous work has shown that kappa opioid agonists can diminish the abuse-related effects and augment the antinociceptive effects of mu agonists. However, use of traditional kappa agonists is limited by their dysphoric side effects.
objectivesThe current study examined the effects of nalfurafine, a clinically available atypical kappa agonist, on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone in male rats.
methodsTo determine oxycodone/nalfurafine mixture proportions to be examined intravenously across procedures, a progressive ratio (PR) self-administration procedure compared the reinforcing effects of oxycodone (56 μg/kg/inj) available alone or as a mixture with co-administered nalfurafine (0.32, 1, or 3.2 μg/kg/inj), corresponding to oxycodone/nalfurafine proportions of 175:1, 56:1, and 18:1, respectively. Next, PR and thermal antinociception dose-effect functions were each determined for oxycodone, nalfurafine, and the same oxycodone/nalfurafine mixture proportions. Finally, the respiratory-depressant effects of equi-antinociceptive doses of oxycodone, nalfurafine, and the mixtures were compared.
resultsNalfurafine decreased the reinforcing effects of oxycodone, and the 18:1 mixture did not function as a reinforcer. Oxycodone and nalfurafine each produced dose-dependent antinociception, and the mixtures produced additive antinociception. In addition, antinociceptive doses of the 56:1 and 18:1 mixtures did not produce respiratory depression.
conclusionsThese results suggest that nalfurafine may augment the thermal antinociceptive effects while reducing the reinforcing and respiratory-depressant effects of oxycodone.
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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.