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7055314 
Journal Article 
Donepezil (Aricept) The World's First Drug for Alzheimer's Disease 
Hara, Y; Kawabe, H; , 
2019 
SPRINGER-VERLAG SINGAPORE PTE LTD 
SINGAPORE 
DRUG DISCOVERY IN JAPAN: INVESTIGATING THE SOURCES OF INNOVATION 
183-205 
WOS:000566291300012 
Donepezil is a symptomatic drug for Alzheimer's disease that was discovered and developed by Eisai Co., Ltd. It has a temporary suppressive effect on the pathology of Alzheimer's disease. Donepezil increases the concentration of acetylcholine, a key neurotransmitter in the brain, by inhibiting the degradative enzyme acetylcholinesterase. While other pharmaceutical groups focused on other mechanisms of action, such as cerebral metabolism improvement or cerebral blood flow improvement, as targets of anti-dementia drug development, the research group at Eisai focused on the acetylcholine hypothesis, for which scientific verification had not been sufficiently carried out. Throughout the research and development process, the difficulty of low bioavailability of lead compounds was encountered and the project was officially suspended within the firm. However, researchers continued to work on the drug. Donepezil was virtually the first drug in its class for Alzheimer's disease in the world, and has long dominated the marketplace as the best-in-class drug, primarily because no better second-generation drugs have been developed. The diffusion of donepezil into the market was also helped by the popularization of MRI scanning, which is effective for early diagnosis and detection of Alzheimer's disease. This has resulted in the accurate diagnosis of patients with Alzheimer's-type dementia, who otherwise may have been diagnosed as having other dementias, thereby expanding the market for donepezil. 
Nagaoka, S; 
978-981-13-8905-4