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Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: An Update in Structure-Activity Relationships.
Curr Med Chem 2018; 25(20):2353-2384CM

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

29332567

Citation

Mustazza, Carlo, et al. "Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: an Update in Structure-Activity Relationships." Current Medicinal Chemistry, vol. 25, no. 20, 2018, pp. 2353-2384.
Mustazza C, Pieretti S, Marzoli F. Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: An Update in Structure-Activity Relationships. Curr Med Chem. 2018;25(20):2353-2384.
Mustazza, C., Pieretti, S., & Marzoli, F. (2018). Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: An Update in Structure-Activity Relationships. Current Medicinal Chemistry, 25(20), pp. 2353-2384. doi:10.2174/0929867325666180111095458.
Mustazza C, Pieretti S, Marzoli F. Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: an Update in Structure-Activity Relationships. Curr Med Chem. 2018;25(20):2353-2384. PubMed PMID: 29332567.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: An Update in Structure-Activity Relationships. AU - Mustazza,Carlo, AU - Pieretti,Stefano, AU - Marzoli,Francesca, PY - 2017/07/24/received PY - 2017/11/30/revised PY - 2017/01/05/accepted PY - 2018/1/16/pubmed PY - 2018/7/24/medline PY - 2018/1/16/entrez KW - G-protein coupled receptors KW - NOP receptor ligands KW - Nociceptin KW - Opioids KW - Pain KW - Structure-activity relationship. SP - 2353 EP - 2384 JF - Current medicinal chemistry JO - Curr. Med. Chem. VL - 25 IS - 20 N2 - 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. SN - 1875-533X UR - https://www.unboundmedicine.com/medline/citation/29332567/Nociceptin_/Orphanin_FQ_Peptide__NOP__Receptor_Modulators:_An_Update_in_Structure_Activity_Relationships_ L2 - http://www.eurekaselect.com/158948/article DB - PRIME DP - Unbound Medicine ER -