Opening the amino acid toolbox for peptide-based NTS2-selective ligands as promising lead compounds for pain management.
neurotensin
opioid-independent analgesic effect
pain management
peptide NTS2-selective ligands
structure-activity relationships
Journal
Journal of peptide science : an official publication of the European Peptide Society
ISSN: 1099-1387
Titre abrégé: J Pept Sci
Pays: England
ID NLM: 9506309
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
revised:
17
12
2022
received:
14
11
2022
accepted:
19
12
2022
medline:
9
5
2023
pubmed:
22
12
2022
entrez:
21
12
2022
Statut:
ppublish
Résumé
Chronic pain is one of the most critical health issues worldwide. Despite considerable efforts to find therapeutic alternatives, opioid drugs remain the gold standard for pain management. The administration of μ-opioid receptor (MOR) agonists is associated with detrimental and limiting adverse effects. Overall, these adverse effects strongly overshadow the effectiveness of opioid therapy. In this context, the development of neurotensin (NT) ligands has shown to be a promising approach for the management of chronic and acute pain. NT exerts its opioid-independent analgesic effects through the binding of two G protein-coupled receptors (GPCRs), NTS1 and NTS2. In the last decades, modified NT analogues have been proven to provide potent analgesia in vivo. However, selective NTS1 and nonselective NTS1/NTS2 ligands cause antinociception associated with hypothermia and hypotension, whereas selective NTS2 ligands induce analgesia without altering the body temperature and blood pressure. In light of this, various structure-activity relationship (SAR) studies provided findings addressing the binding affinity of ligands towards NTS2. Herein, we comprehensively review peptide-based NTS2-selective ligands as a robust alternative for future pain management. Particular emphasis is placed on SAR studies governing the desired selectivity and associated in vivo results.
Substances chimiques
Receptors, Neurotensin
0
Amino Acids
0
Analgesics, Opioid
0
Peptides
0
Neurotensin
39379-15-2
Ligands
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3471Subventions
Organisme : CIHR
ID : FDN-148413
Pays : Canada
Organisme : CIHR
ID : FDN-148413
Pays : Canada
Informations de copyright
© 2022 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.
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