ArticleFrontiers in pharmacology2019
Repeated Administration of Norbinaltorphimine Produces Cumulative Kappa Opioid Receptor Inactivation.
Article in Frontiers in pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Post-traumatic stress disorder: pathogenesis, epidemiological characteristics, animal models, and potential therapeutic strategies.Military Medical Research · 2026Review
- Anesthesia unconsciousness recruits dynamic parabrachial activity within a distributed brain-wide ensemble.bioRxiv : the preprint server for biology · 2026Article
- Kappa opioid receptor antagonism in neuropsychiatry: from molecular mechanisms to clinical prospects.European archives of psychiatry and clinical neuroscience · 2026Review
- G Protein Inactivation as a Mechanism for Addiction Treatment.Biological psychiatry · 2026Article
- Dynorphin modulates reward-seeking actions through a pallido-amygdala cholinergic circuit.Neuron · 2025Article
- The dynorphin/kappa opioid receptor mediates adverse immunological and behavioral outcomes induced by repetitive blast trauma.Journal of neuroinflammation · 2022Article
- Effects of Daily Methocinnamox Treatment on Fentanyl Self-Administration in Rhesus Monkeys.The Journal of pharmacology and experimental therapeutics · 2022Article
- Article
- Nicotine and the developing brain: Insights from preclinical models.Pharmacology, biochemistry, and behavior · 2022Article
- The Role of Dynorphin and the Kappa Opioid Receptor in Schizophrenia and Major Depressive Disorder: A Translational Approach.Handbook of experimental pharmacology · 2022Review
- Release of endogenous dynorphin opioids in the prefrontal cortex disrupts cognition.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Verifying the role of 3-hydroxy of 17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(4'-pyridyl) carboxamido]morphinan derivatives via their binding affinity and selectivity profiles on opioid receptors.Bioorganic chemistry · 2021Article
- Nalfurafine reduces neuroinflammation and drives remyelination in models of CNS demyelinating disease.Clinical & translational immunology · 2021Article
- Regulation of Kappa Opioid Receptor Inactivation Depends on Sex and Cellular Site of Antagonist Action.Molecular pharmacology · 2020Article
- A Review of Strain and Sex Differences in Response to Pain and Analgesia in Mice.Comparative medicine · 2019Review
- Impact of Pharmacological Manipulation of theThe Journal of pharmacology and experimental therapeutics · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Kappa receptor activation by dynorphins contributes to the anxiogenic, dysphoric, and cognitive disrupting effects of repeated stress, suggesting that kappa receptor antagonists might have therapeutic utility in the treatment of stress disorders. Three classes of kappa antagonists have been distinguished: non-selective, selective-competitive (readily reversible), and non-competitive (receptor-inactivating); however, which would be the most effective medication has not been established. To assess the utility of receptor inactivating antagonists, we tested the effects of a range of doses in both male and female mice. As previously established, the antinociceptive effects of the kappa agonist U50,488 were blocked by a single injection of the long-acting antagonist norbinatorphimine (norBNI) (10 mg/kg i.p.) in male mice. Ten to 20-fold lower doses of norBNI were ineffective after a single administration, but daily administration of 1.0 or 0.5 mg/kg for 5 days completely blocked U50,488 antinociceptive effects. Daily administration of 0.1 mg/kg norBNI produced slowly accumulating inhibition and completely blocked the antinociceptive effect of U50,488 after 20-30 days. Estrogen reduces female sensitivity to kappa opioid effects, but 30 days of 0.1 mg/kg norBNI completely blocked U50,488 analgesia in ovariectomized mice. Receptor inactivation in both male and female mice treated for 30 days with 0.1 mg/kg norBNI persisted for at least 1-week. These results suggest that receptor-inactivating kappa antagonists are effective in both males and females when given at 100-fold lower doses than typically administered in preclinical studies. The enhanced safety of this low-dosing protocol has important clinical implications if receptor inactivating kappa antagonists advance in medication development.
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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.