Naldemedine, also known as S 297995, is a peripherally-selective μ-opioid receptor antagonist under development by Shionogi for the treatment of opioid-induced adverse effects including constipation, nausea, and vomiting. Clinical studies have thus far found it to possess statistically significant effectiveness for these indications and to be generally well-tolerated with predominantly mild to moderate gastrointestinal side effects. No effects indicative of central opioid withdrawal or impact on the analgesic or mydriatic effects of co-administered opioids have been observed.
Inagaki M, Kume M, Tamura Y, Hara S, Goto Y, Haga N, Hasegawa T, Nakamura T, Koike K, Oonishi S, Kanemasa T, Kai H. Discovery of naldemedine: A potent and orally available opioid receptor antagonist for treatment of opioid-induced adverse effects. Bioorg Med Chem Lett. 2019 Jan 1;29(1):73-77. doi: 10.1016/j.bmcl.2018.11.007. Epub 2018 Nov 7. PubMed PMID: 30446313.
Tamura, Yoshinori; Noguchi, Kouichi; Inagaki, Masanao; Morimoto, Kenji; Haga, Nobuhiro; Oda, Shinichi; Omura, Sohei. Preparation of crystalline 6,7-unsaturated-7-carbamoyl morphinane derivative, and method for producing same. WO 2012063933. (Assignee Shionogi & Co., Ltd., Japan)
Inagaki, Masanao; Hara, Shin-Ichiro; Haga, Nobuhiro; Tamura, Yoshinori; Goto, Yoshihisa; Hasegawa, Tsuyoshi. Preparation of 6,7-unsaturated-7-carbamoyl substituted morphinan derivatives as opioid antagonists for the treatment of nausea, vomiting and/or constipation. WO 2006126637. (Assignee Shionogi & Co., Ltd., Japan)
