Anti-Alzheimer's Drug, Donepezil, Markedly Improves Long-Term Survival After Chronic Heart Failure in Mice

Donepezil, Therapeutic Acetylcholinesterase Inhibitor, Prevents the Progression of Ventricular Dysfunction by Promoting Myocardial Glucose Utilization in Rat Model of Chronic Heart Failure Following Myocardial Infarction

“…In this study, the dose of donepezil administrated to rats was 5.0 mg/kg/day, which was about 50 times higher than the therapeutic doses used in the clinical setting. However, although different from that used in humans, a daily dose of 5.0 mg/kg has been extensively used in animal studies without any side effects [13,23]. In a preliminary study, we confirmed that this dose of donepezil was the submaximal dose that did not cause side effects such as vomiting, diarrhea, anorexia, or growth retardation.…”

“…This dose may cause slow heartbeat as a side effect [24]. However, we have reported that donepezil exhibits a cardioprotective effect in failing murine hearts in a heart rateindependent manner [10,13]. Also, in the present study, donepezil improved cardiac contractility without slowing heart rate ( Table 1).…”

“…Although donepezil is widely used as an acetylcholinesterase inhibitor for the treatment of Alzheimer's disease [14,15], our experimental studies have demonstrated that donepezil elicits various effects on the cardiovascular system, independent of cholinesterase inhibitory actions [10,12,13]. Without slowing heart rate, donepezil improved long-term survival in animals with CHF through upregulation of anti-apoptotic and angiogenic factors in cardiac and endothelial cells [12,13].…”

“…A series of animal and clinical studies conducted by our group has shown a beneficial effect of donepezil in CHF [6][7][8][9][10][11][12][13]. Although donepezil is widely used as an acetylcholinesterase inhibitor for the treatment of Alzheimer's disease [14,15], our experimental studies have demonstrated that donepezil elicits various effects on the cardiovascular system, independent of cholinesterase inhibitory actions [10,12,13].…”

Donepezil, a potential therapeutic agent for heart failure

“…2,3 A similar result was also obtained by Handa et al in mice with CHF. 4 Chronic administration of donepezil for 2 weeks could not only induce vagal nerve activation, but could also reduce sympathetic nerve activation, as demonstrated by Umegaki and Khookhor in a recent study. 5 Cardiac autonomic imbalance is one of the most important features of CHF.…”