ArticleJournal of pain research2011
Analgesic efficacy of CR4056, a novel imidazoline-2 receptor ligand, in rat models of inflammatory and neuropathic pain.
Article in Journal of pain research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Pharmacology, Medicinal Chemistry, and Therapeutic Potential of Imidazoline Receptor Ligands.ChemMedChem · 2026Review
- Discovery of (3-Phenylcarbamoyl-3,4-dihydro-2Journal of medicinal chemistry · 2025Article
- The imidazoline IPsychopharmacology · 2024Article
- Molecular Modeling, Synthesis, and Antihyperglycemic Activity of the New Benzimidazole Derivatives - Imidazoline Receptor Agonists.Drug design, development and therapy · 2024Article
- Editorial: Women in science: pharmacological treatment of pain.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- 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
- An Imidazoline 2 Receptor Ligand Relaxes Mouse AortaFrontiers in pharmacology · 2022Article
- 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
- Behavioral and Cognitive Improvement Induced by Novel Imidazoline INeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Article
- First evaluation of PET-based human biodistribution and radiation dosimetry ofEJNMMI research · 2018Article
- Mechanisms of imidazoline IBritish journal of pharmacology · 2018Article
- Neuroanatomical characterization of imidazoline IThe European journal of neuroscience · 2018Article
- Role of intracellular CaPsychopharmacology · 2017Article
- Imidazoline IPharmacology & therapeutics · 2017Review
- Tolerance and cross-tolerance to the antinociceptive effects of oxycodone and the imidazoline IPsychopharmacology · 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
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two decades of investigations have failed to unequivocally clarify the functions and the molecular nature of imidazoline-2 receptors (I2R). However, there is robust pharmacological evidence for the functional modulation of monoamino oxidase (MAO) and other important enzyme activities by I2 site ligands. Some compounds of this class proved to be active experimental tools in preventing both experimental pain and opioid tolerance and dependence. Unfortunately, even though these compounds bind with high potency to central I2 sites, they fail to represent a valid clinical opportunity due to their pharmacokinetic, selectivity or side-effects profile. This paper presents the preclinical profile of a novel I2 ligand (2-phenyl-6-(1H-imidazol-1yl) quinazoline; [CR4056]) that selectively inhibits the activity of human recombinant MAO-A in a concentration-dependent manner. A sub-chronic four day oral treatment of CR4056 increased norepinephrine (NE) tissue levels both in the rat cerebral cortex (63.1% ±4.2%; P < 0.05) and lumbar spinal cord (51.3% ± 6.7%; P < 0.05). In the complete Freund's adjuvant (CFA) rat model of inflammatory pain, CR4056 was found to be orally active (ED50 = 5.8 mg/kg, by mouth [p.o.]). In the acute capsaicin model, CR4056 completely blocked mechanical hyperalgesia in the injured hind paw (ED50 = 4.1 mg/kg, p.o.; ED100 = 17.9 mg/kg, p.o.). This effect was dose-dependently antagonized by the non-selective imidazoline I2/α2 antagonist idazoxan. In rat models of neuropathic pain, oral administration of CR4056 significantly attenuated mechanical hyperalgesia and allodynia. In summary, the present study suggests a novel pharmacological opportunity for inflammatory and/or neuropathic pain treatment based on selective interaction with central imidazoline-2 receptors.
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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.