Pharmacological characterization of naloxegol: In vitro and in vivo studies.
Eur J Pharmacol
; 903: 174132, 2021 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-33933466
ABSTRACT
Opioid-induced constipation is the most prevalent adverse effect of opioid drugs. Peripherally acting mu opioid receptor antagonists (PAMORAs), including naloxegol, are indicated for the treatment of opioid-induced constipation. The aim of this study was the in vitro and in vivo pharmacological characterization of naloxegol in comparison with naloxone. In vitro experiments were performed to measure calcium mobilization in cells coexpressing opioid receptors and chimeric G proteins and mu receptor interaction with G protein and ß-arrestin 2 using bioluminescence resonance energy transfer. In vivo experiments were performed in mice to measure pain threshold using the tail withdrawal assay and colonic transit using the bead expulsion assay. In vitro, naloxegol behaved as a selective and competitive mu receptor antagonist similarly to naloxone, being 3-10-fold less potent. In vivo, naloxone was effective in blocking fentanyl actions when given subcutaneously (sc), but not per os (po). In contrast, naloxegol elicited very similar effects with sc or po administration counteracting in a dose dependent manner the constipating effects of fentanyl without interfering with the fentanyl mediated analgesia. Thus, a useful PAMORA action could be obtained with naloxegol both after po and sc administration.
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Bases de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
/
Estreñimiento
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Morfinanos
/
Antagonistas de Narcóticos
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia