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Donepezil, marketed under the trade name Aricept, is a medication used in the palliative treatment of Alzheimer’s disease.
Common side effects include loss of appetite, gastrointestinal upset, diarrhea, difficulty sleeping, vomiting, or muscle cramping.
It was developed by Eisai and Pfizer and is sold as a generic by multiple suppliers. Donepezil acts as a centrally acting reversible acetylcholinesterase inhibitor.
Contents
1 Medical uses
1.1 Alzheimer’s disease
2 Adverse effects
2.1 Precautions
3 Mechanism of action
4 History
5 Research
6 Stereochemistry
7 References
8 External links
Medical uses
Alzheimer’s disease
There is no evidence that donepezil or other similar agents alters the course or progression of Alzheimer’s disease. 6 to 12-month controlled studies have shown modest benefits in cognition and/or behavior.
Adverse effects
In clinical trials the most common adverse events leading to discontinuation were nausea, diarrhea, and vomiting.
Precautions
Donepezil should be used with caution in people with heart disease, cardiac conduction disturbances, chronic obstructive pulmonary disease, asthma, severe cardiac arrhythmias and sick sinus syndrome.
People with peptic ulcer disease or taking NSAIDS should use caution because increased risk of gastrointestinal bleeding was noted.
Mechanism of action
Donepezil binds and reversibly inactivates the cholinesterases, thus inhibiting hydrolysis of acetylcholine. This increases acetylcholine concentrations at cholinergic synapses.
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.
In addition to its actions as an acetylcholinesterase inhibitor, donepezil has been found to act as a potent agonist of the σ 1 receptor (K i = 14.6 nM), and has been shown to produce specific antiamnestic effects in animals mainly via this action.
History
Donepezil inhibiting Torpedo californica acetylcholinesterase.
10 mg Aricept pill
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.
Research
Donepezil has been tested in other cognitive disorders, including Lewy body dementia,
Donepezil has also been studied in patients with mild cognitive impairment, schizophrenia, attention deficit disorder, post- Coronary artery bypass surgery cognitive impairment, At this time, though, donepezil is not indicated for prevention of dementia.
Stereochemistry
Donepezil medications are racemates.
Enantiomers
( R )-Donepezil
( S )-Donepezil

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