Aminoguanidine Hydrazone Derivatives as Nonpeptide NPFF1 Receptor Antagonists Reverse Opioid Induced Hyperalgesia.
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| Abstract |
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.
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| Authors | Hassan Hammoud, Khadija Elhabazi, Raphäelle Quillet, Isabelle Bertin, Valérie Utard, Emilie Laboureyras, Jean-Jacques Bourguignon, Frédéric Bihel, Guy Simonnet, Frédéric Simonin, Martine Schmitt |
| Journal | ACS chemical neuroscience (ACS Chem Neurosci) Vol. 9 Issue 11 Pg. 2599-2609 (11 21 2018) ISSN: 1948-7193 [Electronic] United States |
| PMID | 29727163 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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