ArticleBritish journal of pharmacology2015
Spinal antinociceptive effects of the novel NOP receptor agonist PWT2-nociceptin/orphanin FQ in mice and monkeys.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Synthesis and Pharmacological Characterization of Nociceptin/Orphanin FQ Dimeric Ligands.Journal of medicinal chemistry · 2025Article
- Review
- Spotlight on Nociceptin/Orphanin FQ Receptor in the Treatment of Pain.Molecules (Basel, Switzerland) · 2022Review
- Therapeutic potentials of NOP and MOP receptor coactivation for the treatment of pain and opioid abuse.Journal of neuroscience research · 2022Review
- Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders.International journal of molecular sciences · 2021Review
- Comprehensive overview of biased pharmacology at the opioid receptors: biased ligands and bias factors.RSC medicinal chemistry · 2021Review
- Nociceptin/Orphanin FQ Peptide Receptor-Related Ligands as Novel Analgesics.Current topics in medicinal chemistry · 2020Review
- BU10038 as a safe opioid analgesic with fewer side-effects after systemic and intrathecal administration in primates.British journal of anaesthesia · 2019Article
- Effects of NOP-Related Ligands in Nonhuman Primates.Handbook of experimental pharmacology · 2019Article
- ORLJournal of molecular neuroscience : MN · 2018Article
- Analysis of the distribution of spinal NOP receptors in a chronic pain model using NOP-eGFP knock-in mice.British journal of pharmacology · 2018Article
- Procyanidins attenuate neuropathic pain by suppressing matrix metalloproteinase-9/2.Journal of neuroinflammation · 2018Article
- Synthesis, Biological Evaluation, and SAR Studies of 14β-phenylacetyl Substituted 17-cyclopropylmethyl-7, 8-dihydronoroxymorphinones Derivatives: Ligands With Mixed NOP and Opioid Receptor Profile.Frontiers in psychiatry · 2018Article
- Article
- Pharmacological studies on the NOP and opioid receptor agonist PWT2-[DmtEuropean journal of pharmacology · 2017Article
- Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems.Pharmacological reviews · 2016Review
- Central N/OFQ-NOP Receptor System in Pain Modulation.Advances in pharmacology (San Diego, Calif.) · 2016Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
background and purposeUsing an innovative chemical approach, peptide welding technology (PWT), a tetrabranched derivative of nociceptin/orphanin FQ (N/OFQ) has been generated and pharmacologically characterized. Both in vitro and in vivo PWT2-N/OFQ displayed the same pharmacological profile to the natural ligand. It was more potent and produced longer-lasting effects. The aim of the present study was to investigate the spinal effects of PWT2-N/OFQ in nociceptive and neuropathic pain models in mice and non-human primates. EXPERIMENTAL APPROACH: Tail withdrawal assay in mice and monkeys was used as a nociceptive pain model and mechanical threshold in mice subjected to chronic constriction injury was used as a neuropathic pain model. The antinociceptive effects of spinally administered N/OFQ and PWT2-N/OFQ were assessed in these models. KEY
resultsPWT2-N/OFQ mimicked the spinal antinociceptive effects of N/OFQ both in nociceptive and neuropathic pain models in mice as well as in non-human primates displaying 40-fold higher potency and a markedly prolonged duration of action. The effects of N/OFQ and PWT2-N/OFQ were sensitive to the N/OFQ receptor (NOP) antagonist SB-612111, but not to opioid receptor antagonists. CONCLUSIONS AND IMPLICATIONS: The present study has demonstrated that PWT2-N/OFQ mimicked the antinociceptive effects of the natural peptide in rodents and non-human primates acting as a potent and longer-lasting NOP-selective agonist. More generally, PWT derivatives of biologically active peptides can be viewed as innovative pharmacological tools for investigating those conditions and states in which selective and prolonged receptor stimulation promotes beneficial effects.
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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.