UFP-101, a peptide antagonist selective for the nociceptin/orphanin FQ receptor

CNS Drug Rev. Summer 2005;11(2):97-112. doi: 10.1111/j.1527-3458.2005.tb00264.x.


Nociceptin/orphanin FQ modulates various biological functions at central and peripheral levels by selectively activating a G-protein coupled receptor named N/OFQ peptide (NOP) receptor. For extending our knowledge on the biological roles of the N/OFQ-NOP receptor system the identification of selective NOP ligands, especially antagonists, is mandatory. [Nphe1, Arg14, Lys15] N/OFQ-NH2 (UFP-101) is a novel NOP ligand that was designed by combining, in the same molecule, the [Nphe1] chemical modification which eliminates efficacy and the [Arg14, Lys15] substitution which increases ligand potency and duration of action in vivo. In the present article, we summarize the pharmacological features of UFP-101 as determined in a series of in vitro and in vivo assays. Moreover, some biological actions and possible therapeutic indications of NOP ligands are discussed on the basis of results obtained with UFP-101. Data obtained with this compound were compared with those generated using other NOP antagonists, especially J-113397 and [Nphe1]N/OFQ(1-13)-NH2, receptor or peptide knockout mice and other pharmacological tools useful for blocking N/OFQ - NOP receptor signaling. The analysis of the available data demonstrates that UFP-101 is a useful pharmacological tool for the investigation of the central and peripheral biological functions regulated by the N/OFQ-NOP receptor system and for defining the therapeutic potential of NOP receptor ligands.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cardiovascular System / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Kidney / drug effects
  • Narcotic Antagonists*
  • Nervous System / drug effects*
  • Opioid Peptides / chemistry
  • Opioid Peptides / metabolism
  • Opioid Peptides / pharmacology*
  • Opioid Peptides / therapeutic use
  • Pain / drug therapy
  • Receptors, Opioid / genetics
  • Receptors, Opioid / metabolism
  • Time Factors


  • (Nphe(1),Arg(14),Lys(15))N-OFQ NH(2)
  • Narcotic Antagonists
  • Opioid Peptides
  • Receptors, Opioid
  • nociceptin receptor