ArticleAlcoholism, clinical and experimental research2019
Combination of Clinically Utilized Kappa-Opioid Receptor Agonist Nalfurafine With Low-Dose Naltrexone Reduces Excessive Alcohol Drinking in Male and Female Mice.
Article in Alcoholism, clinical and experimental research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Nalfurafine is Aversive at Antinociceptive Doses in Mice.Pharmacology research & perspectives · 2025Article
- Limitations and potential of κOR biased agonists for pain and itch management.Neuropharmacology · 2024Review
- Systematic Structure-Activity Relationship Study of Nalfurafine Analogues toward Development of Potentially Nonaddictive Pain Management Treatments.Journal of medicinal chemistry · 2024Article
- Systemic kappa opioid receptor antagonism accelerates reinforcement learning via augmentation of novelty processing in male mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Sex- and β-arrestin-dependent effects of kappa opioid receptor-mediated ethanol consumption.Pharmacology, biochemistry, and behavior · 2022Article
- Aticaprant (Clinically Developed Kappa-Opioid Receptor Antagonist) Combined With Naltrexone Prevents Alcohol "Relapse" Drinking.Journal of pharmaceutics & pharmacology · 2022Article
- The Kappa Opioid Receptor: A Promising Therapeutic Target for Multiple Pathologies.Frontiers in pharmacology · 2022Review
- Preclinical Studies on Nalfurafine (TRK-820), a Clinically Used KOR Agonist.Handbook of experimental pharmacology · 2022Article
- Signaling underlying kappa opioid receptor-mediated behaviors in rodents.Frontiers in neuroscience · 2022Review
- Involvement of GRK2 in modulating nalfurafine-induced reduction of excessive alcohol drinking in mice.Neuroscience letters · 2021Article
- Blockade of alcohol excessive and "relapse" drinking in male mice by pharmacological cryptochrome (CRY) activation.Psychopharmacology · 2021Article
- Comparison of Pharmacological Properties between the Kappa Opioid Receptor Agonist Nalfurafine and 42B, Its 3-Dehydroxy Analogue: Disconnect betweenACS chemical neuroscience · 2020Article
- Modulation of cocaine-related behaviors by low doses of the potent KOR agonist nalfurafine in male C57BL6 mice.Psychopharmacology · 2020Article
- mTORC1 pathway is involved in the kappa opioid receptor activation-induced increase in excessive alcohol drinking in mice.Pharmacology, biochemistry, and behavior · 2020Article
- Fluorescence-guided resection of tumors in mouse models of oral cancer.Scientific reports · 2020Article
- Dynorphin and its role in alcohol use disorder.Brain research · 2020Review
- Kappa opioid receptors in the bed nucleus of the stria terminalis regulate binge-like alcohol consumption in male and female mice.Neuropharmacology · 2020Article
- Clinically utilized kappa-opioid receptor agonist nalfurafine combined with low-dose naltrexone prevents alcohol relapse-like drinking in male and female mice.Brain research · 2019Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNalfurafine is the first clinically approved kappa-opioid receptor (KOP-r) agonist as an antipruritus drug with few side effects in humans (e.g., sedation, depression, and dysphoria). No study, however, has been done using nalfurafine on alcohol drinking in rodents or humans.
methodsWe investigated whether nalfurafine alone or in combination with mu-opioid receptor (MOP-r) antagonist naltrexone changed excessive alcohol drinking in male and female C57BL/6J (B6) mice subjected to a chronic intermittent-access drinking paradigm (2-bottle choice, 24-hour access every other day) for 3 weeks. Neuronal proopiomelanocortin enhancer (nPE) knockout mice with brain-specific deficiency of beta-endorphin (endogenous ligand of MOP-r) were used as a genetic control for the naltrexone effects.
resultsSingle administration of nalfurafine decreased alcohol intake and preference in both male and female B6 mice in a dose-dependent manner. Pretreatment with nor-BNI (a selective KOP-r antagonist) blocked the nalfurafine effect on alcohol drinking, indicating a KOP-r-mediated mechanism. Pharmacological effects of a 5-dosing nalfurafine regimen were further evaluated: The repeated nalfurafine administrations decreased alcohol consumption without showing any blunted effects, suggesting nalfurafine did not develop a tolerance after the multidosing regimen tested. Nalfurafine did not produce any sedation (spontaneous locomotor activity), anhedonia-like (sucrose preference test), anxiety-like (elevated plus maze test), or dysphoria-like (conditioned place aversion test) behaviors, suggesting that nalfurafine had few side effects. Investigating synergistic effects between low-dose naltrexone and nalfurafine, we found that single combinations of nalfurafine and naltrexone, at doses lower than individual effective dose, profoundly decreased excessive alcohol intake in both sexes. The effect of nalfurafine on decreasing alcohol consumption was confirmed in nPE-/- mice, suggesting independent mechanisms by which nalfurafine and naltrexone reduced alcohol drinking.
conclusionThe clinically utilized KOP-r agonist nalfurafine in combination with low-dose naltrexone has potential in alcoholism treatment.
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