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. 2006 Jun 7;11(2):97–112. doi: 10.1111/j.1527-3458.2005.tb00264.x

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

Girolamo Calo 1,✉, Remo Guerrini 2, Anna Rizzi 1, Severo Salvadori 2, Melissa Burmeister 3, Daniel R Kapusta 3, David G Lambert 4, Domenico Regoli 1
PMCID: PMC6741746  PMID: 16007234

ABSTRACT

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

Keywords: Knockout mice, Nociceptin/orphanin FQ, NOP antagonists, NOP receptors, Opioids, UFP‐101

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