ArticleBritish journal of pharmacology2010
Spinal or systemic TY005, a peptidic opioid agonist/neurokinin 1 antagonist, attenuates pain with reduced tolerance.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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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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
36 citing papers in PubMed, 56 citations in OpenAlex.
- GαScience signaling · 2025Article
- In Vivo, In Vitro and In Silico Studies of the Hybrid Compound AA3266, an Opioid Agonist/NK1R Antagonist with Selective Cytotoxicity.International journal of molecular sciences · 2020Article
- Neurokinin receptors in drug and alcohol addiction.Brain research · 2020Review
- Genetic and pharmacological antagonism of NKMolecular psychiatry · 2018Article
- Novel Pharmacological Nonopioid Therapies in Chronic Pain.Current pain and headache reports · 2018Review
- Analgesic Properties of Opioid/NK1 Multitarget Ligands with Distinct in Vitro Profiles in Naive and Chronic Constriction Injury Mice.ACS chemical neuroscience · 2017Article
- Novel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain.The Yale journal of biology and medicine · 2017Review
- Hydrazone Linker as a Useful Tool for Preparing Chimeric Peptide/Nonpeptide Bifunctional Compounds.ACS medicinal chemistry letters · 2017Article
- Discovery of Stable Non-opioid Dynorphin A Analogues Interacting at the Bradykinin Receptors for the Treatment of Neuropathic Pain.ACS chemical neuroscience · 2016Article
- BN-9, a chimeric peptide with mixed opioid and neuropeptide FF receptor agonistic properties, produces nontolerance-forming antinociception in mice.British journal of pharmacology · 2016Article
- Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators.Journal of the American Chemical Society · 2016Article
- Article
- Neurokinin 1 and opioid receptors: relationships and interactions in nervous system.Translational perioperative and pain medicine · 2016Article
- Dual Alleviation of Acute and Neuropathic Pain by Fused Opioid Agonist-Neurokinin 1 Antagonist Peptidomimetics.ACS medicinal chemistry letters · 2015Article
- Discovery of Novel Multifunctional Ligands with μ/δ Opioid Agonist/Neurokinin-1 (NK1) Antagonist Activities for the Treatment of Pain.Journal of medicinal chemistry · 2015Article
- Discovery of tripeptide-derived multifunctional ligands possessing delta/mu opioid receptor agonist and neurokinin 1 receptor antagonist activities.Bioorganic & medicinal chemistry letters · 2015Article
- Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist - neurokinin-1 antagonist peptidomimetics.European journal of medicinal chemistry · 2015Article
- The pharmacology of neurokinin receptors in addiction: prospects for therapy.Substance abuse and rehabilitation · 2015Review
- Discovery of amphipathic dynorphin A analogues to inhibit the neuroexcitatory effects of dynorphin A through bradykinin receptors in the spinal cord.Journal of the American Chemical Society · 2014Article
- Investigational peptide and peptidomimetic μ and δ opioid receptor agonists in the relief of pain.Expert opinion on investigational drugs · 2014Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeThe use of opioids in treating pain is limited due to significant side effects including somnolence, constipation, analgesic tolerance, addiction and respiratory depression. Pre-clinical studies have shown that neurokinin 1 (NK(1) ) receptor antagonists block opioid-induced antinociceptive tolerance and may inhibit opioid-induced rewarding behaviours. Here, we have characterized a bifunctional peptide with both opioid agonist and NK(1) antagonist pharmacophores in a rodent model of neuropathic pain. EXPERIMENTAL APPROACH: Rats were evaluated for behavioural responses to both tactile and thermal stimuli in either an uninjured, sham- or nerve-injured state. TY005 (Tyr-DAla-Gly-Phe-Met-Pro-Leu-Trp-O-3,5-Bn(CF(3) )(2) ) was delivered spinally or systemically to assess the antinociceptive effects after acute exposure. Motor skills were evaluated using the rotarod test to determine potential sedative effects. Spinal TY005 was given chronically to sham- or nerve-injured animals to determine the development of tolerance. KEY
resultsBolus injections of TY005 produced dose-dependent antinociception in non-injured animals and alleviated nerve injury-induced thermal and tactile hypersensitivities (i.e. antihyperalgesia) more effectively than morphine. Sedative effects were not evident from the rotarod test at doses that were antihyperalgesic, nor at doses threefold higher. Repeated administration of TY005 did not lead to the development of antihyperalgesic tolerance or alter sensory thresholds. CONCLUSIONS AND IMPLICATIONS: Collectively, the data suggest that opioid agonist/NK(1) antagonist bifunctional peptides represent a promising novel approach to the management of chronic pain without the development of tolerance, reducing the need for escalation of doses and unwanted side effects associated with opiates alone.
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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.