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

Abstract	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.
Authors	Frédéric Simonin, Martine Schmitt, Jean-Paul Laulin, Emilie Laboureyras, Jack H Jhamandas, David MacTavish, Audrey Matifas, Catherine Mollereau, Patrick Laurent, Marc Parmentier, Brigitte L Kieffer, Jean-Jacques Bourguignon, Guy Simonnet
Journal	Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 103 Issue 2 Pg. 466-71 (Jan 10 2006) ISSN: 0027-8424 [Print] United States
PMID	16407169 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Amides Analgesics, Opioid Dipeptides Ligands Receptors, Neuropeptide adamantylcarbonyl-arginyl-phenylalaninamide neuropeptide FF receptor Heroin Adamantane
Topics	Adamantane (analogs & derivatives, chemistry, pharmacology) Amides (chemistry) Analgesics, Opioid (antagonists & inhibitors, pharmacology) Animals Blood Pressure (drug effects) COS Cells Chlorocebus aethiops Dipeptides (chemistry, pharmacology) Drug Tolerance Heart Rate (drug effects) Heroin (antagonists & inhibitors, pharmacology) Humans Hyperalgesia (chemically induced, metabolism, physiopathology) Ligands Molecular Structure Rats Receptors, Neuropeptide (antagonists & inhibitors, metabolism)

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