Trial reportThe international journal of neuropsychopharmacology2014
Determining pharmacological selectivity of the kappa opioid receptor antagonist LY2456302 using pupillometry as a translational biomarker in rat and human.
Trial report in The international journal of neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Safety in treatment: Classical pharmacotherapeutics and new avenues for addressing maternal depression and anxiety during pregnancy.Pharmacological reviews · 2025Review
- Kappa opioid receptor antagonism protects working memory performance from mild stress exposure in Rhesus macaques.Neurobiology of stress · 2022Article
- Pharmacological Treatments for Anhedonia.Current topics in behavioral neurosciences · 2022Article
- In vivo Characterization of the Opioid Receptor-Binding Profiles of Samidorphan and Naltrexone in Rats: Comparisons at Clinically Relevant Concentrations.Neuropsychiatric disease and treatment · 2022Article
- Sex Differences in Protein Kinase A Signaling of the Latent Postoperative Pain Sensitization That Is Masked by Kappa Opioid Receptors in the Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Pre-training naltrexone increases conditioned fear learning independent of adolescent alcohol consumption history.Physiology & behavior · 2021Article
- The kappa opioid receptor antagonist aticaprant reverses behavioral effects from unpredictable chronic mild stress in male mice.Psychopharmacology · 2020Article
- Regulation of Kappa Opioid Receptor Inactivation Depends on Sex and Cellular Site of Antagonist Action.Molecular pharmacology · 2020Article
- A randomized, double-blind, placebo-controlled study of the kappa opioid receptor antagonist, CERC-501, in a human laboratory model of smoking behavior.Addiction biology · 2020Article
- Sex differences in kappa opioid receptor inhibition of latent postoperative pain sensitization in dorsal horn.Neuropharmacology · 2020Article
- Differential effects of novel kappa opioid receptor antagonists on dopamine neurons using acute brain slice electrophysiology.PloS one · 2020Article
- Targeting opioid dysregulation in depression for the development of novel therapeutics.Pharmacology & therapeutics · 2019Review
- Impact of Pharmacological Manipulation of theThe Journal of pharmacology and experimental therapeutics · 2019Article
- Design and Synthesis of a Novel and Selective Kappa Opioid Receptor (KOR) Antagonist (BTRX-335140).Journal of medicinal chemistry · 2019Article
- Repeated Administration of Opra Kappa (LY2456302), a Novel, Short-Acting, Selective KOP-r Antagonist, in Persons with and without Cocaine Dependence.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Reversal of Stress-Induced Social Interaction Deficits by Buprenorphine.The international journal of neuropsychopharmacology · 2018Article
- "Effects of the novel relatively short-acting kappa opioid receptor antagonist LY2444296 in behaviors observed after chronic extended-access cocaine self-administration in rats".Psychopharmacology · 2017Article
- Receptor Occupancy of the κ-Opioid Antagonist LY2456302 Measured with Positron Emission Tomography and the Novel Radiotracer 11C-LY2795050.The Journal of pharmacology and experimental therapeutics · 2016Article
- Article
- "Does the opioid system block or enhance the antidepressant effects of ketamine?"Chronic stress (Thousand Oaks, Calif.)Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSelective kappa opioid receptor antagonism is a promising experimental strategy for the treatment of depression. The kappa opioid receptor antagonist, LY2456302, exhibits ~30-fold higher affinity for kappa opioid receptors over mu opioid receptors, which is the next closest identified pharmacology.
methodsHere, we determined kappa opioid receptor pharmacological selectivity of LY2456302 by assessing mu opioid receptor antagonism using translational pupillometry in rats and humans.
resultsIn rats, morphine-induced mydriasis was completely blocked by the nonselective opioid receptor antagonist naloxone (3mg/kg, which produced 90% mu opioid receptor occupancy), while 100 and 300 mg/kg LY2456302 (which produced 56% and 87% mu opioid receptor occupancy, respectively) only partially blocked morphine-induced mydriasis. In humans, fentanyl-induced miosis was completely blocked by 50mg naltrexone, and LY2456302 dose-dependently blocked miosis at 25 and 60 mg (minimal-to-no blockade at 4-10mg).
conclusionsWe demonstrate, for the first time, the use of translational pupillometry in the context of receptor occupancy to identify a clinical dose of LY2456302 achieving maximal kappa opioid receptor occupancy without evidence of significant mu receptor antagonism.
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