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Preventing Donepezil-Induced Adverse Effects Through N-acetylcysteine Co-Administration
Jiae Park1, Jung-Pyo Oh1, Kyojin Ku1
1DR. NOAH Biotech Inc., Suwon, Republic of Korea.
Journal of Alzheimer'S Disease : JAD
|September 20, 2024
Summary
N-acetylcysteine (NAC) alleviates donepezil-induced adverse effects in rats by reducing muscle cell oxidative stress and calcium overload. This finding may improve Alzheimer's disease treatment compliance.
Area of Science:
- Pharmacology
- Neuroscience
- Toxicology
Background:
- Drug-induced adverse symptoms significantly impact patient quality of life (QoL) and treatment compliance.
- Alzheimer's disease (AD) treatments often require long-term use, making side effect management crucial.
- Donepezil, a common Alzheimer's drug, causes side effects, particularly at higher doses.
Purpose of the Study:
- To identify a compound that can mitigate donepezil's side effects.
- To investigate the mechanisms underlying donepezil-induced adverse effects and their attenuation.
Main Methods:
- Rats were administered donepezil and N-acetylcysteine (NAC) daily for four weeks.
- Adverse symptoms were monitored, and in vitro studies assessed calcium influx and reactive oxygen species (ROS) in muscle cells.
Main Results:
- NAC co-treatment significantly reduced donepezil-induced adverse symptoms in rats.
- Donepezil increased ROS and intracellular calcium ([Ca2+]i) in muscle cells.
- NAC effectively lowered ROS and [Ca2+]i levels in muscle cells.
Conclusions:
- NAC diminishes donepezil's adverse effects by regulating ROS and [Ca2+]i in skeletal muscle.
- This mechanism suggests NAC could improve donepezil treatment efficacy and patient QoL in Alzheimer's disease.
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