|Systematic (IUPAC) name|
|Oral tablet, 5,10 & 23mg|
|Biological half-life||70 hours|
|CAS Registry Number|
|PDB ligand ID||E20 (, )|
|Molecular mass||379.492 g/mol|
|(what is this?)|
Donepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, and now sold as a generic by multiple suppliers, is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the palliative treatment of Alzheimer's disease. Common side effects include gastrointestinal upset. It has an oral bioavailability of 100% and easily crosses the blood–brain barrier. Because it has a biological half-life of about 70 hours, it can be taken once a day.
Currently, no definitive proof shows the use of donepezil or other similar agents alters the course or progression of Alzheimer's disease (AD). However, 6 to 12-month controlled studies have shown modest benefits in cognition and/or behavior. The UK National Institute for Clinical Excellence (NICE) recommends donepezil as an option in the management of mild to moderate Alzheimer's disease. The person should, however, be reviewed frequently and if there is no significant benefit it should be stopped.
Donepezil should be used with caution in people with cardiac disease, cardiac conduction disturbances, chronic obstructive pulmonary disease, asthma, severe cardiac arrhythmias and sick sinus syndrome.
Patients with gastrointestinal disorders should use caution because nausea or vomiting may occur. These symptoms may appear more frequent when initiating treatment or increasing the donepezil dose. Although occurrence of seizures is rare, patients who have a predisposition to seizures should be treated with caution.
Mechanism of action
The precise mechanism of action of donepezil in patients with Alzheimer's disease is not fully understood. Certainly Alzheimer's disease involves a substantial loss of the elements of the cholinergic system and it is generally accepted that the symptoms of Alzheimer’s disease are related to this cholinergic deficit, particularly in the cerebral cortex and other areas of the brain. It is noted that the hippocampal formation plays an important role in the processes of control of attention, memory and learning. Just the severity of the loss of cholinergic neurons of the central nervous system (CNS) has been found to correlate with the severity of cognitive impairment. Donepezil binds and inactivates reversibly the cholinesterases, thus inhibiting hydrolysis of acetylcholine. This results in an increased acetylcholine concentrations at cholinergic synapses.
Donepezil has been tested (off label) in other cognitive disorders, including Lewy body dementia, and vascular dementia, but it is not currently approved for these indications. Donepezil has also been found to improve sleep apnea in Alzheimer's patients. It also improves gait in patient with mild Alzheimer's Disease. 
Donepezil has also been studied in patients with mild cognitive impairment, schizophrenia, attention deficit disorder, post-Coronary artery bypass surgery cognitive impairment, cognitive impairment associated with multiple sclerosis, CADASIL syndrome, and Down syndrome. A three-year National Institutes of Health trial in patients with mild cognitive impairment reported donepezil was superior to placebo in delaying rate of progression to dementia during the initial 18 months of the study, but this was not sustained at 36 months. In a secondary analysis, a subgroup of individuals with the apolipoprotein E4 genotype showed sustained benefits with donepezil throughout the study. At this time, though, donepezil is not indicated for prevention of dementia.
A 2001 study suggested that donepezil can improve speech in autistic children. The study found the speech of autistic children that was originally mildly to moderately affected appeared to improve with the use of donepezil.
Development and marketing
Research leading to the development of donepezil began in 1983 at Eisai, and in 1996, Eisai received approval from the United States Food and Drug Administration (USFDA) for donepezil under the brand Aricept, which it co-marketed with Pfizer. As of 2011, Aricept was the world's best-selling Alzheimer's disease treatment. The first generic donepezil became available in November 2010 with the USFDA approval of a formulation prepared by Ranbaxy Labs. In April 2011 a second generic formulation, from Wockhardt, received tentative USFDA marketing approval.
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- Montero-Odasso, Manuel; Muir-Hunter, Susan W.; Oteng-Amoako, Afua; Gopaul, Karen; Islam, Anam; Borrie, Michael; Wells, Jennie; Speechley, Mark (2015-01-01). "Donepezil improves gait performance in older adults with mild Alzheimer's disease: a phase II clinical trial". Journal of Alzheimer's disease: JAD 43 (1): 193–199. doi:10.3233/JAD-140759. ISSN 1875-8908. PMID 25079803.
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- Kanoko Matsuyama (25 April 2011). "Eisai Aricept Patch for Alzheimer’s Isn’t Ready for Approval". Bloomberg. Retrieved 25 April 2011.
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- Brenner, George D.; George M., PhD. Brenner (2000). Pharmacology. Philadelphia: W. B. Saunders. ISBN 0-7216-7757-6.
- Acting Editor-in-Chief Louise Welbanks. (2000). Compendium of Pharmaceuticals and Specialities, 2000 (25th ed.). Canadian Pharmaceutical Assn. ISBN 0-919115-76-4.
- Official Aricept product site
- Aricept entry at Drugs.com
- 3D Molecular structure of Donepezil
- Acetylcholinesterase: A gorge-ous enzyme QUite Interesting PDB Structure article at PDBe