Development of a peptidomimetic antagonist of neuropeptide FF receptors for the prevention of opioid-induced hyperalgesia.
ACS Chem. Neurosci.. 2015-02-07; 6(3): 438-445
DOI: 10.1021/cn500219h
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1. ACS Chem Neurosci. 2015 Mar 18;6(3):438-45. doi: 10.1021/cn500219h. Epub 2015 Feb
7.
Development of a peptidomimetic antagonist of neuropeptide FF receptors for the
prevention of opioid-induced hyperalgesia.
Bihel F(1), Humbert JP(2), Schneider S(1), Bertin I(2), Wagner P(1), Schmitt
M(1), Laboureyras E(3), Petit-Demoulière B(4), Schneider E(5), Mollereau C(6),
Simonnet G(3), Simonin F(2), Bourguignon JJ(1).
Author information:
(1)†University of Strasbourg, CNRS, UMR7200, Faculty of pharmacy, 67400 Illkirch
Graffenstaden, France.
(2)‡University of Strasbourg, CNRS, UMR7242, ESBS, 67412 Illkirch Graffenstaden,
France.
(3)§University of Bordeaux Ségalen, INCIA, CNRS UMR5287, 33076 Bordeaux, France.
(4)∥Institut Clinique de la Souris, University of Strasbourg, 67404 Illkirch,
France.
(5)⊥Phenopro, 67400 Illkirch, France.
(6)#University of Toulouse, CNRS, UMR5089, IPBS, 31077 Toulouse, France.
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.
DOI: 10.1021/cn500219h
PMID: 25588572 [Indexed for MEDLINE]