Characterization of 17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(indole-7-carboxamido)morphinan (NAN) as a Novel Opioid Receptor Modulator for Opioid Use Disorder Treatment.
Analgesics, Opioid
/ chemistry
Animals
Dose-Response Relationship, Drug
Mice
Morphinans
/ chemistry
Narcotic Antagonists
/ pharmacology
Opioid-Related Disorders
/ drug therapy
Receptors, Opioid, delta
/ antagonists & inhibitors
Receptors, Opioid, kappa
/ antagonists & inhibitors
Receptors, Opioid, mu
/ antagonists & inhibitors
Thalamus
/ drug effects
NAN
Opioid use disorder
mixed function ligand
naltrexamine
opioid antagonist
μ opioid receptors
Journal
ACS chemical neuroscience
ISSN: 1948-7193
Titre abrégé: ACS Chem Neurosci
Pays: United States
ID NLM: 101525337
Informations de publication
Date de publication:
15 05 2019
15 05 2019
Historique:
pubmed:
14
2
2019
medline:
30
5
2020
entrez:
14
2
2019
Statut:
ppublish
Résumé
The opioid crisis is a significant public health issue with more than 115 people dying from opioid overdose per day in the United States. The aim of the present study was to characterize the in vitro and in vivo pharmacological effects of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(indole-7-carboxamido)morphinan (NAN), a μ opioid receptor (MOR) ligand that may be a potential candidate for opioid use disorder treatment that produces less withdrawal signs than naltrexone. The efficacy of NAN was compared to varying efficacy ligands at the MOR, and determined at the δ opioid receptor (DOR) and κ opioid receptor (KOR). NAN was identified as a low efficacy partial agonist for G-protein activation at the MOR and DOR, but had relatively high efficacy at the KOR. In contrast to high efficacy MOR agonists, NAN did not induce MOR internalization, downregulation, or desensitization, but it antagonized agonist-induced MOR internalization and stimulation of intracellular Ca
Identifiants
pubmed: 30758946
doi: 10.1021/acschemneuro.9b00038
pmc: PMC6520168
mid: NIHMS1014658
doi:
Substances chimiques
17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-6-((4'-(3'-methylpyridyl))carboxamido)morphinan
0
Analgesics, Opioid
0
Morphinans
0
Narcotic Antagonists
0
Receptors, Opioid, delta
0
Receptors, Opioid, kappa
0
Receptors, Opioid, mu
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2518-2532Subventions
Organisme : NIDA NIH HHS
ID : P30 DA013429
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA024022
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA045274
Pays : United States
Organisme : NIDA NIH HHS
ID : F31 DA043921
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA041359
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA044855
Pays : United States
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