Fundamental research for the application of a novel kappa opioid receptor agonist for medical treatment of pain relief

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06796
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: National Cancer Center Japan (2023); University of Tsukuba (2021)
• Principal Investigator: Nagumo Yasuyuki 国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (00459661)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 新規オピオイド鎮痛薬 / κオピオイド受容体作動薬 / 疼痛緩和

Outline of Final Research Achievements

In this study, we investigated whether a novel kappa opioid receptor (KOR) agonist, rationally designed to distinguish between its analgesic dose and the dose that induces side effects (sedation and drug aversion), is both effective and safe for pain management. The compound demonstrated analgesic effects against hyperalgesia, including cancer pain, and within its analgesic dose range, it did not induce sedative or aversive effects. Furthermore, in chronic treatment study, the development of tolerance to present compound-induced analgesic effects was weaker than that of other KOR agonist and morphine. Additionally, it is found that the combination of present KOR agonist and mu-opioid agonist morphine has additive or synergic analgesic effects. These results indicate a potential basis for the acquisition of preclinical proof-of-concept as the first KOR agonist to develop a clinically applicable analgesic.

Free Research Field

緩和医療

Academic Significance and Societal Importance of the Research Achievements

臨床使用されるオピオイド鎮痛薬は、ほとんどがμオピオイド受容体作動薬であり、吐き気や便秘、傾眠や呼吸抑制などの副作用の他、疼痛下ではほとんど問題とならないが、非疼痛下では強い依存性を示すことが問題となっている。特に、欧米では依存性が深刻な社会問題となっている。従って、本化合物の様な薬物依存性や嫌悪性といった精神作用を示さない新規のオピオイド化合物は、社会的薬物依存問題への歯止めになる可能性があり、さらに鎮痛薬としては、鎮静作用などの副作用に対する安全性が高い化合物として、医師の処方ならびに患者の服用を見込める可能性がある。