{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:17:59Z","timestamp":1777393079614,"version":"3.51.4"},"reference-count":51,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2024,10,8]]},"abstract":"<jats:p>Background: Drug-induced adverse symptoms affect patients\u2019 quality of life (QoL) during treatment. Understanding the underlying mechanisms of drug-induced adverse effects could help prevent them. As current drugs have limited effects in halting the progress of Alzheimer\u2019s disease (AD), patients are required to take these drugs over a long period. The main obstacles to long-term compliance are drug-elicited side effects that deteriorate patient QoL. Objective: Donepezil, the most popular acetylcholinesterase inhibitor (AChEI) drug for AD, induces various side effects, especially at high doses. This study aimed to identify a drug that can attenuate the side effects of donepezil and investigate the underlying mechanisms. Methods: Five-week-old Sprague-Dawley rats received daily oral donepezil and N-acetylcysteine (NAC) for four weeks. General symptoms following administration were monitored daily to address drug-related adverse effects. Cytosolic calcium influx and generation of reactive oxygen species (ROS) after drug treatment were measured in vitro using C2C12 myotubes. Results: High-dose donepezil induced numerous adverse symptoms in male and female rats, which were markedly attenuated by co-treatment with NAC. NAC significantly reduced both acute and chronic muscle-related symptoms caused by donepezil. Additionally, in vitro studies showed that high-dose donepezil increased ROS and intracellular calcium ([Ca2+]i) levels in muscle cells, contributing to these adverse effects. NAC co-treatment dramatically reduced ROS and [Ca2+]i levels in muscle cells. Conclusions: Combined treatment with NAC effectively diminishes the adverse effects elicited by donepezil by regulating ROS and [Ca2+]i levels in the skeletal muscle, which could contribute to improving donepezil treatment in patients.<\/jats:p>","DOI":"10.3233\/jad-240709","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T13:12:28Z","timestamp":1728393148000},"page":"1281-1292","source":"Crossref","is-referenced-by-count":2,"title":["Preventing Donepezil-Induced Adverse Effects Through N-acetylcysteine Co-Administration"],"prefix":"10.1177","volume":"101","author":[{"given":"Jiae","family":"Park","sequence":"first","affiliation":[{"name":"DR. NOAH Biotech Inc., Suwon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Pyo","family":"Oh","sequence":"additional","affiliation":[{"name":"DR. NOAH Biotech Inc., Suwon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyojin","family":"Ku","sequence":"additional","affiliation":[{"name":"DR. NOAH Biotech Inc., Suwon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeonsun","family":"Jin","sequence":"additional","affiliation":[{"name":"DR. NOAH Biotech Inc., Suwon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"DR. NOAH Biotech Inc., Suwon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"DR. 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