Naloxegol-d5 is intended for use as an internal standard for the quantification of naloxegol by GC- or LC-MS. Naloxegol is a peripherally acting antagonist of the μ-opioid receptor (Ki = 7.42 nM; pA2 = 7.95).1 It is selective for the μ-opioid receptor over the δ-opioid receptor (Ki = 866 nM). Naloxegol also acts as a partial agonist of κ-opioid receptors in vitro (EC50 = 47 nM for [35S]GTPγS binding) but lacks activity ex vivo at concentrations up to 10 μM. In vivo, naloxegol reverses morphine-induced decreases in gastrointestinal motility and analgesia in a hot-plate assay in rats (ED50s = 23.1 and 55.4 mg/kg, respectively), demonstrating a two-fold separation for peripheral versus CNS effects. Naloxegol also exhibits a brain uptake rate comparable to atenolol, a low-permeation standard with no brain uptake, in a rat brain perfusion model.
|1. Floettmann, E., Bui, K., Sostek, M., et al. Pharmacologic profile of naloxegol, a peripherally acting μ-opioid receptor antagonist, for the treatment of opioid-induced constipation. J. Pharmacol. Exp. Ther. 361(2), 280-291 (2017).