Identification of an N -acylated- D Arg-Leu-NH 2 Dipeptide as a Highly Selective Neuropeptide FF1 Receptor Antagonist That Potently Prevents Opioid-Induced Hyperalgesia
| Autor: | Patrick Gizzi, Brigitte Ilien, Raphaëlle Quillet, Valérie Kugler, Frédéric Simonin, Valérie Simonneaux, Martine Schmitt, Frédéric Bihel, Khadija Elhabazi, Valérie Utard, Jo B. Henningsen, Armand Drieu la Rochelle, Séverine Schneider |
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| Přispěvatelé: | Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Laboratoire d'Innovation Thérapeutique (LIT), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Plate-forme de chimie biologique intégrative de Strasbourg (PCBiS), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), ANR-17-EURE-0022,EURIDOL,Ecole Universitaire de Recherche Interdisciplinaire sur la Douleur(2017), ANR-10-LABX-0034,Medalis,Medalis Drug Discovery Center(2010) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Chemistry medicine.drug_class Antagonist Chronic pain Neuropeptide Pharmacology Receptor antagonist medicine.disease 01 natural sciences 3. Good health 0104 chemical sciences 010404 medicinal & biomolecular chemistry 03 medical and health sciences Drug Discovery Hyperalgesia medicine Molecular Medicine [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Neuropeptide FF medicine.symptom Receptor Opioid-induced hyperalgesia ComputingMilieux_MISCELLANEOUS 030304 developmental biology |
| Zdroj: | Journal of Medicinal Chemistry Journal of Medicinal Chemistry, American Chemical Society, 2021, 64 (11), pp.7555-7564. ⟨10.1021/acs.jmedchem.1c00256⟩ |
| ISSN: | 0022-2623 1520-4804 |
| Popis: | RFamide-related peptide-3 (RFRP-3) and neuropeptide FF (NPFF) target two different receptor subtypes called neuropeptide FF1 (NPFF1R) and neuropeptide FF2 (NPFF2R) that modulate several functions. However, the study of their respective role is severely limited by the absence of selective blockers. We describe here the design of a highly selective NPFF1R antagonist called RF3286, which potently blocks RFRP-3-induced hyperalgesia in mice and luteinizing hormone release in hamsters. We then showed that the pharmacological blockade of NPFF1R in mice prevents the development of fentanyl-induced hyperalgesia while preserving its analgesic effect. Altogether, our data indicate that RF3286 represents a useful pharmacological tool to study the involvement of the NPFF1R/RFRP-3 system in different functions and different species. Thanks to this compound, we showed that this system is critically involved in the development of opioid-induced hyperalgesia, suggesting that NPFF1R antagonists might represent promising therapeutic tools to improve the use of opioids in the treatment of chronic pain. |
| Databáze: | OpenAIRE |
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