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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

Naldemedine: Peripherally Acting Opioid Receptor Antagonist for Treating Opioid-induced Adverse Effects

Author(s): Masanao Inagaki*, Toshiyuki Kanemasa and Takaaki Yokota

Volume 20, Issue 31, 2020

Page: [2830 - 2842] Pages: 13

DOI: 10.2174/1568026620666200710105953

Price: $65

Abstract

Opioids are widely used for pain management in moderate-to-severe pain. However, opioids are associated with adverse events, such as constipation and emesis/vomiting. To reduce these undesired effects, a structure–activity relationship study of morphinan derivatives was conducted, and a promising lead compound with inhibitory effects on opioid receptors was obtained. Further improvement in the potency and pharmacokinetic profiles of the lead compound led to the discovery of naldemedine, which showed anti-constipation and anti-emetic effects against these adverse events that were induced by morphine without influencing morphine’s analgesic effect. Naldemedine was launched in Japan and the USA in 2017 and in the EU in 2019, for treating opioid-induced constipation.

Keywords: Opioid receptor, Dual antagonist, OIC, OINV, Naldemedine, Peripherally-acting.

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