UFP-101, a Peptide Antagonist Selective for the Nociceptin/Orphanin FQ Receptor

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