The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Jun 2020
Pharmacological Profile of Naldemedine, a Peripherally Acting μ-Opioid Receptor Antagonist: Comparison with Naloxone and Naloxegol.
Opioid-induced constipation (OIC), a typical side effect of opioids, is due to activation of the μ-opioid receptors in the enteric nervous system. Peripherally acting μ-opioid receptor antagonists (PAMORAs) can reverse OIC by inhibiting the peripheral action of opioids without affecting centrally mediated analgesia. Naldemedine is a PAMORA with potent antagonist activity against μ-, δ-, and κ-opioid receptors. ⋯ Naldemedine showed a noncompetitive antagonism and slower association and dissociation kinetics against μ-opioid receptors than naloxone and naloxegol. Naldemedine showed insurmountable antagonism of morphine-induced inhibition and lower and slower peripheral withdrawal symptoms (diarrhea) than the other compounds. Therefore, naldemedine has a different pharmacological profile (the type of antagonism and binding kinetics) to the other compounds.