ArticleThe international journal of neuropsychopharmacology2019
Behavioral Pharmacology of Novel Kappa Opioid Receptor Antagonists in Rats.
Article in The international journal of neuropsychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Trial
- Effects of behavioral interventions on stress reactivity in adults with substance use disorders.Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors · 2024Trial
- Xylazine reduces methamphetamine-induced hyperlocomotion in rats through κ-opioid and α2-adrenoceptor mechanisms.Neuroscience letters · 2026Article
- Brixadi for Stimulant Use Disorder: Evolving Pharmacologic Considerations and Clinical Implications.Advances in therapy · 2026Review
- Kappa opioid receptor antagonism in neuropsychiatry: from molecular mechanisms to clinical prospects.European archives of psychiatry and clinical neuroscience · 2026Review
- Kappa opioid receptors diminish spontaneous dopamine signals in awake mice through multiple mechanisms.Neuropharmacology · 2025Article
- Supraspinal kappa-opioid receptors: new therapeutic strategies for pain, pruritus, and negative emotions.Experimental brain research · 2025Article
- Unlocking opioid neuropeptide dynamics with genetically encoded biosensors.Nature neuroscience · 2024Article
- The Antidepressant Effect of Magnolol on Depression-Like Behavior of CORT-Treated Mice.Journal of molecular neuroscience : MN · 2024Article
- Interactions between thePhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
- An analog of [d-Trp]CJ-15,208 exhibits kappa opioid receptor antagonism following oral administration and prevents stress-induced reinstatement of extinguished morphine conditioned place preference.Pharmacology, biochemistry, and behavior · 2022Article
- Aticaprant (Clinically Developed Kappa-Opioid Receptor Antagonist) Combined With Naltrexone Prevents Alcohol "Relapse" Drinking.Journal of pharmaceutics & pharmacology · 2022Article
- Pharmacology of Kappa Opioid Receptors: Novel Assays and Ligands.Frontiers in pharmacology · 2022Article
- Kappa Opioid Receptor Antagonists as Potential Therapeutics for Mood and Substance Use Disorders.Handbook of experimental pharmacology · 2022Article
- KOR Control over Addiction Processing: An Exploration of the Mesolimbic Dopamine Pathway.Handbook of experimental pharmacology · 2022Article
- Beneficial Effects of Opioid Rotation to Buprenorphine/Naloxone on Opioid Misuse, Craving, Mental Health, and Pain Control in Chronic Non-Cancer Pain Patients with Opioid Use Disorder.Journal of clinical medicine · 2021Article
- Improving the Utility of a Dynorphin Peptide Analogue Using Mannosylated Glycoliposomes.International journal of molecular sciences · 2021Article
- Chronic opioid exposure differentially modulates oxycodone self-administration in male and female rats.Addiction biology · 2021Article
- New agents and perspectives in the pharmacological treatment of major depressive disorder.Progress in neuro-psychopharmacology & biological psychiatry · 2021Review
- Evaluation of Antinociceptive Effects of Chitosan-Coated Liposomes Entrapping the Selective Kappa Opioid Receptor Agonist U50,488 in Mice.Medicina (Kaunas, Lithuania) · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundNew treatments for stress-related disorders including depression, anxiety, and substance use disorder are greatly needed. Kappa opioid receptors are expressed in the central nervous system, including areas implicated in analgesia and affective state. Although kappa opioid receptor agonists share the antinociceptive effects of mu opioid receptor agonists, they also tend to produce negative affective states. In contrast, selective kappa opioid receptor antagonists have antidepressant- and anxiolytic-like effects, stimulating interest in their therapeutic potential. The prototypical kappa opioid receptor antagonists (e.g., norBNI, JDTic) have an exceptionally long duration of action that complicates their use in humans, particularly in tests to establish safety. This study was designed to test dose- and time-course effects of novel kappa opioid receptor antagonists with the goal of identifying short-acting lead compounds for future medication development.
methodsWe screened 2 novel, highly selective kappa opioid receptor antagonists (CYM-52220 and CYM-52288) with oral efficacy in the warm water tail flick assay in rats to determine initial dose and time course effects. For comparison, we tested existing kappa opioid receptor antagonists JDTic and LY-2456302 (also known as CERC-501 or JNJ-67953964).
resultsIn the tail flick assay, the rank order of duration of action for the antagonists was LY-2456302 < CYM-52288 < CYM-52220 << JDTic. Furthermore, LY-2456302 blocked the depressive (anhedonia-producing) effects of the kappa opioid receptor agonist U50,488 in the intracranial self-stimulation paradigm, albeit at a higher dose than that needed for analgesic blockade in the tail flick assay.
conclusionsThese results suggest that structurally diverse kappa opioid receptor antagonists can have short-acting effects and that LY-2456302 reduces anhedonia as measured in the intracranial self-stimulation test.
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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.