Development of a peptidomimetic antagonist of neuropeptide FF receptors for the prevention of opioid-induced hyperalgesia.

Abstract

Through the development of a new class of unnatural ornithine derivatives as bioisosteres of arginine, we have designed an orally active peptidomimetic antagonist of neuropeptide FF receptors (NPFFR). Systemic low-dose administration of this compound to rats blocked opioid-induced hyperalgesia, without any apparent side-effects. Interestingly, we also observed that this compound potentiated opioid-induced analgesia. This unnatural ornithine derivative provides a novel therapeutic approach for both improving analgesia and reducing hyperalgesia induced by opioids in patients being treated for chronic pain.

• Authors: Frédéric Bihel, Jean-Paul Humbert, Séverine Schneider, Isabelle Bertin, Patrick Wagner, Martine Schmitt, Emilie Laboureyras, Benoît Petit-Demoulière, Elodie Schneider, Catherine Mollereau, Guy Simonnet, Frédéric Simonin, Jean-Jacques Bourguignon
• Journal: ACS chemical neuroscience (ACS Chem Neurosci) Vol. 6 Issue 3 Pg. 438-45 (Mar 18 2015) ISSN: 1948-7193 [Electronic] United States
• PMID: 25588572 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Peptidomimetics
• Receptors, Neuropeptide
• neuropeptide FF receptor
• Tritium
• Arginine
• Cyclic AMP
• Ornithine
• Fentanyl

Topics

• Analgesics, Opioid (toxicity)
• Animals
• Arginine (metabolism)
• Chemical Phenomena
• Cyclic AMP (metabolism)
• Fentanyl (toxicity)
• HEK293 Cells
• Humans
• Hyperalgesia (chemically induced, prevention & control)
• Male
• Microsomes, Liver (drug effects, metabolism)
• Ornithine (metabolism)
• Pain Threshold (drug effects)
• Peptidomimetics (chemistry, therapeutic use)
• Protein Binding (drug effects)
• Rats
• Rats, Sprague-Dawley
• Receptors, Neuropeptide (antagonists & inhibitors, metabolism)
• Structure-Activity Relationship
• Time Factors
• Tritium (pharmacokinetics)