Metabolically stable neurotensin analogs exert potent and long-acting analgesia without hypothermia.
Antinociception
Chronic pain
JMV431 (Pubchem SID 135652223)
Metabolic stability
NT(8-13) (PubChem CID 5311318)
PD149163 (PubChem CID 73064239)
Silaproline
TMSAla
Unnatural amino acid
Journal
Behavioural brain research
ISSN: 1872-7549
Titre abrégé: Behav Brain Res
Pays: Netherlands
ID NLM: 8004872
Informations de publication
Date de publication:
07 05 2021
07 05 2021
Historique:
received:
01
07
2020
revised:
10
02
2021
accepted:
11
02
2021
pubmed:
20
2
2021
medline:
27
1
2022
entrez:
19
2
2021
Statut:
ppublish
Résumé
The endogenous tridecapeptide neurotensin (NT) has emerged as an important inhibitory modulator of pain transmission, exerting its analgesic action through the activation of the G protein-coupled receptors, NTS1 and NTS2. Whereas both NT receptors mediate the analgesic effects of NT, NTS1 activation also produces hypotension and hypothermia, which may represent obstacles for the development of new pain medications. In the present study, we implemented various chemical strategies to improve the metabolic stability of the biologically active fragment NT(8-13) and assessed their NTS1/NTS2 relative binding affinities. We then determined their ability to reduce the nociceptive behaviors in acute, tonic, and chronic pain models and to modulate blood pressure and body temperature. To this end, we synthesized a series of NT(8-13) analogs carrying a reduced amide bond at Lys
Identifiants
pubmed: 33607165
pii: S0166-4328(21)00077-2
doi: 10.1016/j.bbr.2021.113189
pii:
doi:
Substances chimiques
Analgesics
0
Neurotensin
39379-15-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113189Subventions
Organisme : CIHR
ID : FDN-148413
Pays : Canada
Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.