RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia

F Simonin, M Schmitt, JP Laulin… - Proceedings of the …, 2006 - National Acad Sciences
F Simonin, M Schmitt, JP Laulin, E Laboureyras, JH Jhamandas, D MacTavish, A Matifas…
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
Neuropeptide FF (NPFF) has been proposed to play a role in pain modulation, opioid
tolerance, and several other physiological processes. However, pharmacological agents
that would help define physiological roles for this peptide are still missing. Here we report
the discovery of a potent and selective NPFF receptor antagonist, RF9, that can be
administered systemically. This compound does not show any effects by itself but can block
efficiently the increase in blood pressure and heart rate evoked by NPFF. When chronically …
Neuropeptide FF (NPFF) has been proposed to play a role in pain modulation, opioid tolerance, and several other physiological processes. However, pharmacological agents that would help define physiological roles for this peptide are still missing. Here we report the discovery of a potent and selective NPFF receptor antagonist, RF9, that can be administered systemically. This compound does not show any effects by itself but can block efficiently the increase in blood pressure and heart rate evoked by NPFF. When chronically coinjected with heroin, RF9 completely blocks the delayed and long-lasting paradoxical opioid-induced hyperalgesia and prevents the development of associated tolerance. Our data indicate that NPFF receptors are part of a bona fide antiopioid system and that selective antagonists of these receptors could represent useful therapeutic agents for improving the efficacy of opioids in chronic pain treatment.
National Acad Sciences