Management of intolerable pain: development of novel methods for the persistent analgesia by simultaneous activation of heterodimerized Gi-coupled receptors

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590740
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: National Cancer Center Japan
• Principal Investigator: UEZONO Yasuhito 独立行政法人国立がん研究センター, 研究所, 分野長 (20213340)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 医療用麻薬 / 難治性疼痛 / Gi蛋白共役型受容体 / 二量体化受容体 / 耐性形成 / モルヒネ / 脱感作 / バクロフェン

Outline of Final Research Achievements

As for the project "development of novel drugs that specifically and selectively activate heterodimeric opioid receptors", we performed in vitro assay regarding the effects of several opioid analgesics on the activity of μ, δ, and κ opioid receptors, by using cells that stably express individual opioid receptors as well as cells co-expressing born μ and δ opioid receptors. By this assay we are going to develop a novel, specific drug that activates heterodimeric opioid receptors. We next investigated "the development of novel drugs that have less opioid tolerance keeping strong analgesic activity", by administration of a combination of small amounts of morphine and baclofen, a μ agonist and a GABAB agonist, respectively. We found that such combination indeed elicited μ and GABAB receptor activity with less receptor desensitization properties. Based on the results, we will pursue innovation of novel methods for analgesic treatment with less opioid tolerance.

Free Research Field

緩和医療学、神経薬理学