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.
Calo
Girolamo
G
Department Experimental and Clinical Medicine, Section of Pharmacology and Neuroscience Centre, University of Ferrara, via Fossato di Mortara, 19, 44100 Ferrara, Italy. g.calo@unife.it
Guerrini
Remo
R
Rizzi
Anna
A
Salvadori
Severo
S
Burmeister
Melissa
M
Kapusta
Daniel R
DR
Lambert
David G
DG
Regoli
Domenico
D
D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007668:Kidney / Q000187:drug effects; D009292:Narcotic Antagonists; D009420:Nervous System / Q000187:drug effects*; D018847:Opioid Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D000094942:Nociceptin Receptor
C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2); D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human