Analysis of the mechanisms underlying inhibition of voltage-gated sodium channel aimed at development of selective inhibitor on Nav1.3

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462462
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: SATA Takeyoshi 産業医科大学, 大学病院, 病院長 (60128030)
• Co-Investigator(Kenkyū-buntansha): HORISHITA Takafumi 産業医科大学, 医学部, 准教授 (40369070)
• Co-Investigator(Renkei-kenkyūsha): OKURA Dan 産業医科大学, 医学部, 助教 (00596710)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 神経障害性疼痛 / 電位依存性ナトリウムチャネル / Nav1.3サブユニット / Nav1.3選択的阻害薬 / 新たな鎮痛薬開発

Outline of Final Research Achievements

We investigated the effects of antidepressants as conventional medications for neuropathic pain, and allopregnanolone sulfate, the metabolite of allopregnanolone that is desired as a new medication for neuropathic pain on voltage-gated sodium channel α subunit, Nav1.3 electrophysiologically in order to contribute the development of selective Nav1.3 inhibitor as a new analgesic for neuropathic pain. We found that these compounds inhibit the function of Nav1.3 dose-dependently. Moreover, we demonstrated that these inhibitory effects were enhanced by co-expression with β3 subunit. These results would help to clarify the mechanisms underlying inhibition of Nav1.3 function, and contribute the development of selective Nav1.3 inhibitor.

Free Research Field

麻酔科学