Aminoguanidine hydrazone derivatives as non-peptide NPFF1 receptor antagonists reverse opioid induced hyperalgesia.
Fiche publication
Date publication
mai 2018
Journal
ACS chemical neuroscience
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SIMONIN Frédéric
Tous les auteurs :
Hammoud H, Elhabazi K, Quillet R, Bertin I, Utard V, Laboureyras E, Bourguignon JJ, Bihel F, Simonnet G, Simonin F, Schmitt M
Lien Pubmed
Résumé
Neuropeptide FF receptors (NPFF1R and NPFF2R) and their endogenous ligand Neuropeptide FF have been shown previously to display anti-opioid 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 on a series of heterocycles as rigidified non-peptide NPFF receptor ligands, starting from already described aminoguanidine hydrazones (AGH's). Binding experiments and functional assays highlighted AGH 1n and its rigidified analog 2-amino-dihydropyrimidine 22e for in vivo experiments. As earlier shown 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 towards NPFF1R.
Mots clés
GPCR, GPR74, aminoguanidine hydrazone, neuropeptide FF, opioid-induced hyperalgesia
Référence
ACS Chem Neurosci. 2018 May 4;: