Development of a peptidomimetic antagonist of neuropeptide FF receptors for the prevention of opioid-induced hyperalgesia.
Fiche publication
Date publication
mars 2015
Journal
ACS chemical neuroscience
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SIMONIN Frédéric
Tous les auteurs :
Bihel F, Humbert JP, Schneider S, Bertin I, Wagner P, Schmitt M, Laboureyras E, Petit-Demoulière B, Schneider E, Mollereau C, Simonnet G, Simonin F, Bourguignon JJ
Lien Pubmed
Résumé
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.
Mots clés
Analgesics, Opioid, toxicity, Animals, Arginine, metabolism, Chemical Phenomena, Cyclic AMP, metabolism, Fentanyl, toxicity, HEK293 Cells, Humans, Hyperalgesia, chemically induced, Male, Microsomes, Liver, drug effects, Ornithine, metabolism, Pain Threshold, drug effects, Peptidomimetics, chemistry, Protein Binding, drug effects, Rats, Rats, Sprague-Dawley, Receptors, Neuropeptide, antagonists & inhibitors, Structure-Activity Relationship, Time Factors, Tritium, pharmacokinetics
Référence
ACS Chem Neurosci. 2015 Mar;6(3):438-45