Functional significance of target molecule of cognitive enhancer ST101 and drug development

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293124
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Tohoku University
• Principal Investigator: Fukunaga Kohji 東北大学, 薬学研究科(研究院), 教授 (90136721)
• Co-Investigator(Kenkyū-buntansha): FUKUDA TAKAICHI 熊本大学, 大学院生命科学研究部, 教授 (50253414) ; MORIGUCHI SHIGEKI 東北大学, 大学院薬学研究科, 講師 (70374949)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: アルツハイマー病 / Ｔ型カルシウムチャネル / アミロイドβ / アセチルコリン / 嗅球摘出マウス

Outline of Final Research Achievements

After structure optimization of ST101 as cognitive enhancer, we developed the novel spiro-imidazopyridine derivative, SAK3. Oral administration of SAK3 (0.5mg/kg) enhanced hippocampal acetylcholine release through T-type calcium channels. In olfactory bulbectomized mice, oral administration of SAK3 improved cognitive function by activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the hippocampus. We next treated Alzheimer model mice APP23 with SAK3 (0.5mg/kg) for three months. The SAK3 treatment inhibited amyloid beat protein accumulation, thereby improving cognitive dysfunction. We also established evaluation protocol of pharmacodynamics after oral administration in rats. Overall, we conduct preclinical studies of SAK3 for safety and pharmacodynamic properties.

Free Research Field

神経薬理学