Pharmacologic effects of naldemedine, a peripherally acting μ-opioid receptor antagonist, in in vitro and in vivo models of opioid-induced constipation.

ABSTRACT:

Background

Naldemedine (S-297995) is a peripherally acting μ-opioid receptor antagonist developed as a once-daily oral drug for opioid-induced constipation (OIC) in adults with chronic noncancer or cancer pain. This study characterized the pharmacological effects of naldemedine in vitro and in vivo.

Methods

The binding affinity and antagonist activity of naldemedine against recombinant human μ-, δ-, and κ-opioid receptors were assayed in vitro. Pharmacologic effects of naldemedine were investigated using animal models of morphine-induced inhibition of small and large intestinal transit, castor oil-induced diarrhea, antinociception, and morphine withdrawal.

Key results

Naldemedine showed potent binding affinity and antagonist activities for recombinant human μ-, δ-, an

SUBMITTER: Kanemasa T 

PROVIDER: S-EPMC6850587 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature