Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators

An Update in Structure-Activity Relationships

Research output: Contribution to journalReview article

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.

Original languageEnglish
Pages (from-to)2353-2384
Number of pages32
JournalCurrent Medicinal Chemistry
Volume25
Issue number20
DOIs
Publication statusPublished - 2018

Fingerprint

Peptide Receptors
Structure-Activity Relationship
Modulators
Peptides
Analgesics
Pressure regulation
Neuroimaging
Antitussive Agents
nociceptin receptor
nociceptin
Overactive Urinary Bladder
Pharmacokinetics
Urination
Anti-Anxiety Agents
Blood pressure
Neurology
Opioid Receptors
G-Protein-Coupled Receptors
Constriction
Pharmaceutical Preparations

Keywords

  • Analgesics/chemistry
  • Animals
  • Humans
  • Molecular Structure
  • Receptors, Opioid/agonists
  • Structure-Activity Relationship

Cite this

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title = "Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: An Update in Structure-Activity Relationships",
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.",
keywords = "Analgesics/chemistry, Animals, Humans, Molecular Structure, Receptors, Opioid/agonists, Structure-Activity Relationship",
author = "Carlo Mustazza and Stefano Pieretti and Francesca Marzoli",
note = "Copyright{\circledC} Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.",
year = "2018",
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language = "English",
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pages = "2353--2384",
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issn = "0929-8673",
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TY - JOUR

T1 - Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators

T2 - An Update in Structure-Activity Relationships

AU - Mustazza, Carlo

AU - Pieretti, Stefano

AU - Marzoli, Francesca

N1 - Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

PY - 2018

Y1 - 2018

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.

AB - 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.

KW - Analgesics/chemistry

KW - Animals

KW - Humans

KW - Molecular Structure

KW - Receptors, Opioid/agonists

KW - Structure-Activity Relationship

U2 - 10.2174/0929867325666180111095458

DO - 10.2174/0929867325666180111095458

M3 - Review article

VL - 25

SP - 2353

EP - 2384

JO - Current Medicinal Chemistry

JF - Current Medicinal Chemistry

SN - 0929-8673

IS - 20

ER -