Involvement of the Peripheral µ-Opioid Receptor in Tramadol-Induced Constipation in Rodents.
Biol Pharm Bull
; 44(11): 1746-1751, 2021.
Article
em En
| MEDLINE
| ID: mdl-34719650
ABSTRACT
Tramadol is a weak opioid that produces analgesic effect via both the µ-opioid receptor (MOR) and non-opioid targets. Constipation is the most common opioid-related side effect in patients with cancer and non-cancer pain. However, the contribution of MOR to tramadol-induced constipation is unclear. Therefore, we used naldemedine, a peripherally acting MOR antagonist, and MOR-knockout mice to investigate the involvement of peripheral MOR in tramadol-induced constipation using a small intestinal transit model. A single dose of tramadol (3-100 mg/kg, per os (p.o.)) inhibited small intestinal transit dose-dependently in rats. Naldemedine (0.01-10 mg/kg, p.o.) blocked the inhibition of small intestinal transit induced by tramadol (30 mg/kg, p.o.) in rats. The transition rate increased dose-dependently over the range of naldemedine 0.01-0.3 mg/kg, and complete recovery was observed at 0.3-10 m/kg. Additionally, tramadol (30 and 100 mg/kg, subcutaneously (s.c.)) inhibited small intestinal transit in wild-type mice but not in MOR-knockout mice. These results suggest that peripheral MOR participates in tramadol-induced constipation.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tramadol
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Receptores Opioides mu
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Constipação Induzida por Opioides
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Analgésicos Opioides
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article