Aminoguanidine Hydrazone Derivatives as Nonpeptide NPFF1 Receptor Antagonists Reverse Opioid Induced Hyperalgesia.

Autor: Hammoud H; University of Strasbourg, CNRS, UMR7200, Faculty of Pharmacy, F-67401 Illkirch Graffenstaden , France., Elhabazi K; Université de Strasbourg, CNRS, Biotechnologie et Signalisation Cellulaire, UMR 7242, F-67401 Illkirch Graffenstaden , France., Quillet R; Université de Strasbourg, CNRS, Biotechnologie et Signalisation Cellulaire, UMR 7242, F-67401 Illkirch Graffenstaden , France., Bertin I; Université de Strasbourg, CNRS, Biotechnologie et Signalisation Cellulaire, UMR 7242, F-67401 Illkirch Graffenstaden , France., Utard V; Université de Strasbourg, CNRS, Biotechnologie et Signalisation Cellulaire, UMR 7242, F-67401 Illkirch Graffenstaden , France., Laboureyras E; Homéostasie-Allostasie-Pathologie-Réhabilitation, UMR 5287 CNRS, Université de Bordeaux, 33076 Bordeaux , France., Bourguignon JJ; University of Strasbourg, CNRS, UMR7200, Faculty of Pharmacy, F-67401 Illkirch Graffenstaden , France., Bihel F; University of Strasbourg, CNRS, UMR7200, Faculty of Pharmacy, F-67401 Illkirch Graffenstaden , France., Simonnet G; Homéostasie-Allostasie-Pathologie-Réhabilitation, UMR 5287 CNRS, Université de Bordeaux, 33076 Bordeaux , France., Simonin F; Université de Strasbourg, CNRS, Biotechnologie et Signalisation Cellulaire, UMR 7242, F-67401 Illkirch Graffenstaden , France., Schmitt M; University of Strasbourg, CNRS, UMR7200, Faculty of Pharmacy, F-67401 Illkirch Graffenstaden , France.
Jazyk: angličtina
Zdroj: ACS chemical neuroscience [ACS Chem Neurosci] 2018 Nov 21; Vol. 9 (11), pp. 2599-2609. Date of Electronic Publication: 2018 May 16.
DOI: 10.1021/acschemneuro.8b00099
Abstrakt: Neuropeptide FF receptors (NPFF1R and NPFF2R) and their endogenous ligand neuropeptide FF have been shown previously to display antiopioid properties and to play a critical role in the adverse effects associated with chronic administrations of opiates including the development of opioid-induced hyperalgesia and analgesic tolerance. In this work, we sought to identify novel NPFF receptors ligands by focusing our interest in a series of heterocycles as rigidified nonpeptide NPFF receptor ligands, starting from already described aminoguanidine hydrazones (AGHs). Binding experiments and functional assays highlighted AGH 1n and its rigidified analogue 2-amino-dihydropyrimidine 22e for in vivo experiments. As shown earlier with the prototypical dipeptide antagonist RF9, both 1n and 22e reduced significantly the long lasting fentanyl-induced hyperalgesia in rodents. Altogether these data indicate that AGH rigidification maintains nanomolar affinities for both NPFF receptors, while improving antagonist character toward NPFF1R.
Databáze: MEDLINE
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