UFP-112 a potent and long-lasting agonist selective for the Nociceptin/Orphanin FQ receptor

Abstract

Nociceptin/orphanin FQ (N/OFQ) controls several biological functions via selective activation of the N/OFQ peptide receptor (NOP). [(pF)Phe(4) Aib(7) Arg(14) Lys(15) ]N/OFQ-NH(2) (UFP-112) is an NOP receptor ligand designed using a combination of several chemical modifications in the same peptide sequence that increase NOP receptor affinity/potency and/or reduce susceptibility to enzymatic degradation. In the present review article, we summarize data from the literature and present original findings on the in vitro and in vivo pharmacological features of UFP-112. Moreover, important biological actions and possible therapeutic indications of NOP receptor agonists are discussed based on the results obtained with UFP-112 and compared with other peptide and nonpeptide NOP receptor ligands.

Figure 1

Chemical structure of nonpeptide NOP receptor agonists (top row) and antagonists (bottom row).

Figure 2

Primary structure of UFP‐112.

Figure 3

Typical tracing showing the kinetics of the inhibitory effects of equieffective concentrations of N/OFQ and UFP‐112 in the electrically stimulated mouse vas deferens.

Figure 4

Cumulative food intake following i.c.v. injection of different doses of N/OFQ (top panel) and UFP‐112 (bottom panel). Values are means ± sem of four separate experiments. *P< 0.05 versus control, according to ANOVA followed by Dunnett test for multiple comparisons. *indicates that all the data points of the relative treatment are statistically different from control.

Figure 5

Thirty‐minute food intake in rats treated with 0.05 nmol UFP‐112 i.c.v. at different times (1–8 h) before access to food. Values are means ± sem of four separate experiments. *P < 0.05 versus control, according to the Student's t‐test for unpaired data.

Figure 6

Cumulative food intake following i.c.v. injection of 0.05 nmol UFP‐112 alone or with 2×20 nmol UFP‐101 (the first injection 15 min before and the second just before injection of UFP‐112). Values are means ± sem of four separate experiments. *P < 0.05 versus control, according to ANOVA followed by Dunnett test for multiple comparisons.