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Journal articles
Aminoguanidine Hydrazone Derivatives as Nonpeptide NPFF1 Receptor Antagonists Reverse Opioid Induced Hyperalgesia
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.
Cited literature [51 references]
https://hal-upec-upem.archives-ouvertes.fr/hal-02323065
Contributor : Martine Schmitt <>
Submitted on : Tuesday, October 22, 2019 - 1:09:25 PM
Last modification on : Wednesday, May 27, 2020 - 4:44:04 PM
Contributor : Martine Schmitt <>
Submitted on : Tuesday, October 22, 2019 - 1:09:25 PM
Last modification on : Wednesday, May 27, 2020 - 4:44:04 PM