Anti-Alzheimer drug donepezil is not cardiodepressive but cardioprotective.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670080
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Kochi University
• 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)
• 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)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 臨床薬学

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.

Free Research Field

循環制御学、医工学