Critical Assessment of G Protein-Biased Agonism at the µ-Opioid Receptor.
Trends Pharmacol Sci
; 41(12): 947-959, 2020 12.
Article
en En
| MEDLINE
| ID: mdl-33097283
ABSTRACT
G protein-biased agonists of the µ-opioid receptor (MOPr) have been proposed as an improved class of opioid analgesics. Recent studies have been unable to reproduce the original experiments in the ß-arrestin2-knockout mouse that led to this proposal, and alternative genetic models do not support the G protein-biased MOPr agonist hypothesis. Furthermore, assessment of putatively biased ligands has been confounded by several factors, including assay amplification. As such, the extent to which current lead compounds represent mechanistically novel, extremely G protein-biased agonists is in question, as is the underlying assumption that ß-arrestin2 mediates deleterious opioid effects. Addressing these current challenges represents a pressing issue to successfully advance drug development at this receptor and improve upon current opioid analgesics.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores Opioides mu
/
Analgésicos Opioides
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Trends Pharmacol Sci
Año:
2020
Tipo del documento:
Article
País de afiliación:
Australia