| Budget Amount *help |
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| 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.
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