The response of the autonomic nervous system to the cholinesterase inhibitor, donepezil.
OBJECTIVE
Donepezil, a cholinesterase inhibitor (ChEI) that is widely used to treat Alzheimer's disease, is thought to act by increasing extracellular acethylcholine (ACh) in the central nervous system. The effects of the administration of ChEIs on the autonomic nervous system, however, are complex and controversial.


METHODS
In this study we observed the effects of donepezil at a dose of 3 mg/kg intraperitoneally (i.p.) on the autonomic nervous system for two weeks using heart rate variability (HRV). In HRV, the high frequency (HF) band is influenced by cardiac parasympathetic tone, and the low frequency (LF) band is influenced by both sympathetic and parasympathetic activity. The ratio of LF and HF (LF/HF) is used for the assessment of the sympathetic nervous system.


RESULTS
In the current study the LF/HF was found to be significantly increased by day 1, but the magnitude of the response gradually decreased. The absolute power of HF increased after an i.p of donepezil of 3 mg daily in groups treated for 1 week and for 2 weeks compared to the single-dose groups.


CONCLUSIONS
Our results suggested that ChEI administration induced sympathetic nervous activation acutely, but chronic administration induced parasympathetic activation.
Department of Geriatrics Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. umegaki@med.nagoya-u.ac.jp.
Hiroyuki
H
Umegaki
Oyun
O
Khookhor
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D000077265:Donepezil; D006339:Heart Rate / Q000187:drug effects*; D007189:Indans / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil