Open AccessRF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia
Author(s) -
Frédéric Simonin,
Martine Schmitt,
JeanPaul Laulin,
Emilie Laboureyras,
Jack H. Jhamandas,
David MacTavish,
Audrey Matifas,
Catherine Mollereau,
Patrick Laurent,
Marc Parmentier,
Brigitte L. Kieffer,
JeanJacques Bourguig,
Guy Simonnet
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0502090103
Subject(s) - hyperalgesia , pharmacology , antagonist , opioid , receptor , opioid receptor , drug tolerance , neuropeptide , opioid antagonist , receptor antagonist , medicine , chemistry , nociception , (+) naloxone
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.