ArticleBritish journal of pharmacology2014
Modulation of imidazoline I2 binding sites by CR4056 relieves postoperative hyperalgesia in male and female rats.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Pharmacology, Medicinal Chemistry, and Therapeutic Potential of Imidazoline Receptor Ligands.ChemMedChem · 2026Review
- The imidazoline IPsychopharmacology · 2024Article
- Molecular Modeling, Synthesis, and Antihyperglycemic Activity of the New Benzimidazole Derivatives - Imidazoline Receptor Agonists.Drug design, development and therapy · 2024Article
- I2-Imidazoline Ligand CR4056 Improves Memory, Increases ApoE Expression and Reduces BBB Leakage in 5xFAD Mice.International journal of molecular sciences · 2022Article
- Modulation of NMDA receptor activity by CR4056, an imidazoline-2 receptor ligand with analgesic properties.Frontiers in pain research (Lausanne, Switzerland) · 2022Article
- Intravenous patient-controlled analgesia plus psychoeducational intervention for acute postoperative pain in patients with pulmonary nodules after thoracoscopic surgery: a retrospective cohort study.BMC anesthesiology · 2021Article
- Improved efficacy, tolerance, safety, and abuse liability profile of the combination of CR4056 and morphine over morphine alone in rodent models.British journal of pharmacology · 2020Article
- CR4056, a powerful analgesic imidazoline-2 receptor ligand, inhibits the inflammation-induced PKCε phosphorylation and membrane translocation in sensory neurons.British journal of pharmacology · 2020Article
- Effects of imidazoline I2 receptor agonists on reserpine-induced hyperalgesia and depressive-like behavior in rats.Behavioural pharmacology · 2019Article
- Imidazoline IPharmacology & therapeutics · 2017Review
- Tolerance and cross-tolerance to the antinociceptive effects of oxycodone and the imidazoline IPsychopharmacology · 2017Article
- Postoperative pain-from mechanisms to treatment.Pain reports · 2017Article
- Efficacy of CR4056, a first-in-class imidazoline-2 analgesic drug, in comparison with naproxen in two rat models of osteoarthritis.Journal of pain research · 2017Article
- Antinociceptive Interactions between the Imidazoline I2 Receptor Agonist 2-BFI and Opioids in Rats: Role of Efficacy at the μ-Opioid Receptor.The Journal of pharmacology and experimental therapeutics · 2016Article
- Interactions between imidazoline I2 receptor ligands and acetaminophen in adult male rats: antinociception and schedule-controlled responding.Psychopharmacology · 2016Article
- Anti-hyperalgesic effects of imidazoline I2 receptor ligands in a rat model of inflammatory pain: interactions with oxycodone.Psychopharmacology · 2015Article
- Individual differences in acute pain-induced endogenous analgesia predict time to resolution of postoperative pain in the rat.Anesthesiology · 2015Article
- Discriminative stimulus effects of the imidazoline I2 receptor ligands BU224 and phenyzoline in rats.European journal of pharmacology · 2015Article
- Discriminative stimulus effects of the novel imidazoline I₂ receptor ligand CR4056 in rats.Scientific reports · 2014Article
- The imidazoline receptors and ligands in pain modulation.Indian journal of pharmacologyReview
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Authors and funding
5 authors.
Funding
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Abstract
background and purposeCR4056 is a novel imidazoline-2 (I2 ) ligand exhibiting potent analgesic activity in animal models of pain. In this study, we investigated the effects of CR4056 in a well-established model of postoperative pain where rats develop hyperalgesia in the injured hind paw. EXPERIMENTAL APPROACH: By measuring paw withdrawal threshold to mechanical pressure, we studied the pharmacology of CR4056, potential sex differences in pain perception and response to treatment, and the pharmacodynamic interaction of CR4056 with morphine. KEY
resultsOral CR4056 and subcutaneous morphine dose-dependently reversed the hyperalgesic response. Analgesic effects of CR4056 were completely suppressed by the non-selective imidazoline I2 /α2 -adrenoceptor antagonist idazoxan, were partially reduced (~30%; P < 0.05) by the selective α2 -adrenoceptor antagonist yohimbine, but were not influenced by the non-selective I1 /α2 -adrenoceptor antagonist efaroxan or by the μ opioid receptor antagonist naloxone. We found no differences in responses to CR4056 or morphine between male and female rats. However, females had a lower pain threshold than males, and needed lower doses of drugs to reach a significant analgesia. When CR4056 and morphine were combined, their median effective doses were lower than expected for additive effects, both in males and in females. Isobolographic analysis confirmed a synergism between CR4056 and morphine. CONCLUSIONS AND IMPLICATIONS: CR4056 is a novel pharmacological agent under development for postoperative pain both as stand-alone treatment and in association with morphine. CR4056 has successfully completed Phase I studies for tolerability and pharmacokinetics in healthy volunteers, and is currently entering the first proof-of-concept study in patients.
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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.