Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: An Update in Structure-Activity Relationships

Title:Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: An Update in Structure-Activity Relationships

Volume: 25 Issue: 20

Author(s): Carlo Mustazza*, Stefano Pieretti and Francesca Marzoli

Affiliation:

• National Centre for Control and Evaluation of Medicines, Italian National Institute of Health, Viale Regina Elena 299, 00161 Roma,Italy

Keywords: Nociceptin, NOP receptor ligands, Opioids, Structure-activity relationship, G-protein coupled receptors, Pain.

Abstract: Nociceptin /Orphanin FQ Peptide” receptor (NOPr) is a G-protein-coupled receptor with the nociceptin/orphanin FQ peptide (N/OFQ) as endogenous agonist. It is expressed in the nervous system as well as in some non-neural tissues. Its activation has pronociceptive effect at the supraspinal level, whereas at the spinal level it produces nociceptive effects at low doses and antinociceptive effects at higher doses. NOPr is also involved in mood and blood pressure regulation, immunoregulation, airway constriction, feeding, urination, bowel motility, learning and memory. Selective NOPr agonists have been tested clinically as anxiolytics and antitussives, and the antagonists as analgesics, antidepressants and in the treatment of alcohol addiction. Two NOPr radioligands have also been tested in humans as neuroimaging agents. Furthermore, the partial agonist peptide SER100 and N/OFQ have been used in clinical trials, respectively for congestive heart failure and overactive bladder. The evidence of interactions between NOP and μ-opioid receptor (MOPr) receptors has been exploited in the use of mixed NOPr/MOPr modulators as analgesics and in the treatment of drug addiction. These drugs are devoid of typical opioid liabilities. In this review, we outline the latest advances in the structure-activity relationships (SAR) of NOPr agonists and antagonists, with emphasis on affinity, activity, selectivity and pharmacokinetic features.

Cite this article as:

Mustazza Carlo *, Pieretti Stefano and Marzoli Francesca, Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: An Update in Structure-Activity Relationships, Current Medicinal Chemistry 2018; 25 (20) . https://dx.doi.org/10.2174/0929867325666180111095458