| Project/Area Number |
26670080
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Kochi University |
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Principal Investigator |
SATO Takayuki 高知大学, 教育研究部医療学系基礎医学部門, 教授 (90205930)
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| Co-Investigator(Renkei-kenkyūsha) |
ARIKAWA Mikihiko 高知大学, 教育研究部自然科学系理学部門, 准教授 (20432817)
NOGUCHI Tatsuya 高知大学, 教育研究部医療学系臨床医学部門, 助教 (50566495)
YAMASAKI Fumiyasu 高知大学, 医学部附属病院, 特任教授 (10243841)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 臨床薬学 |
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| Outline of Final Research Achievements |
Our previous studies reported that an oral low dose of donepezil, an acetylcholinesterase (AChE) inhibitor against Alzheimer’s disease, prevented ventricular remodeling and dysfunction after large myocardial infarction in rats without a bradycardiac effect, and that vagal nerve stimulation protected the heart against ischemia-induced ventricular tachyarrhythmias independent of a heart rate-slowing mechanism.
This study demonstrated that pretreatment with acetylcholine (ACh), a neurotransmitter of cardiac vagal nerve endings, salvaged in vitro cardiomyocytes from prolonged hypoxia-induced cell death by preserving mitochondrial function and activating cell survival signals including PI3K/Akt/HIF-1α/VEGF and that ACh prevented hypoxia-induced loss of gap-junction channels to maintain cell-to-cell communication and electrical stability.
From these results, we conclude that donepezil is a potent anti-heart failure drug.
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