Donepezil
730754
225166315
2008-07-12T06:35:39Z
ImperfectlyInformed
5106682
adding a couple references
{{drugbox
| IUPAC_name = 2-[(1-benzyl-4-piperidyl)methyl]- 5,6-dimethoxy-2,3-dihydroinden-1-one
| image = Donepezil skeletal.svg
| image2= Donepezil3d.png
| CAS_number = 120014-06-4
| ATC_prefix = N06
| ATC_suffix = DA02
| ATC_supplemental =
| PubChem = 3152
| DrugBank = APRD00039
| C=24 | H=29 | N=1 | O=3
| molecular_weight = 379.492 g/mol
| smiles = COc1cc2c(CC(CC3CCN(CC3)Cc3ccccc3)C2=O)cc1OC
| bioavailability = 100 (%)
| protein_bound = 96%
| metabolism =
| elimination_half-life = 70 hours
| pregnancy_category =
| legal_status = Rx
| routes_of_administration = Oral tablet, 5 & 10 mg
| excretion = 0,11-0,13 (l/h/kg)
}}
'''Donepezil''', marketed under the trade name '''Aricept''' ([[Eisai Co.|Eisai]]), is a centrally acting reversible [[acetylcholinesterase inhibitor]]. Its main therapeutic use is in the treatment of [[Alzheimer's disease]] where it is used to increase cortical [[acetylcholine]]. It has an [[oral bioavailability]] of 100% and easily crosses the [[blood-brain barrier]]. Because it has a [[half life]] of about 70 hours, it can be taken once a day. Initial dose is 5 mg per day, which can be increased to 10 mg per day after an adjustment period of at least 4 weeks.
==Studies in Alzheimer's disease==
[[Image:AChE inhibited by donepezil 1EVE.png|thumb|Donepezil inhibiting [[Pacific electric ray|''Torpedo californica'']] acetylcholinesterase. From {{PDB|1EVE}}.]]
Currently, there is no definitive proof that use of donepezil or other similar agents alters the course or progression of Alzheimer's disease. However, 6-12 month controlled studies have shown modest benefits in cognition and/or behavior, such as one published in 1999.<ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2328349 Is donepezil effective for treating Alzheimer's disease?]</ref> Pilot studies have reported that donepezil therapy may potentially have effects on markers of disease progression, such as [[hippocampal]] volume. Therefore, many neurologists, psychiatrists, and primary care physicians use donepezil in patients with Alzheimer's disease. In 2005, the UK [[National Institute for Health and Clinical Excellence|National Institute for Clinical Excellence]] (NICE) withdrew its recommendation for use of the drug for mild-to-moderate AD, on the basis that there is no significant improvement in functional outcome; of quality of life or of behavioral symptoms. However, NICE revised its guidelines to suggest that donepezil be used in moderate stage patients for whom the evidence is strongest.<ref>{{cite journal |author=Xiong G, Doraiswamy PM |title=Combination drug therapy for Alzheimer's disease: what is evidence-based, and what is not? |journal=Geriatrics |volume=60 |issue=6 |pages=22–6 |year=2005 |pmid=15948662 |doi=}}</ref>
While the drug is currently indicated for mild to moderate Alzheimer's, there is also evidence from 2 trials that it may be effective for moderate to severe disease. An example of this is a [[Karolinska Institute]] paper published in ''[[The Lancet]]'' in early 2006, which states that donepezil improves cognitive function even in patients with severe Alzheimer's disease symptoms. <ref>{{cite web |url=http://news.bbc.co.uk/2/hi/health/4832574.stm |title=Drug 'treats severe Alzheimer's' |accessdate=2007-07-24 |format= |work=}}</ref>
==Combinations==
Donepezil is sometimes used in combination with [[memantine]], a newer agent for Alzheimer's disease, as the response to both together is considered superior to donepezil alone. In moderate to severe Alzheimer's, a controlled clinical trial has shown that the addition of Memantine to stable donepezil therapy improves cognition, functioning and behavior.
==Uses for other conditions==
Donepezil has been tested in other cognitive disorders including [[Lewy body dementia]] and [[vascular dementia]], but it is not currently approved for these indications. Donepezil has also been studied in patients with [[mild cognitive impairment|Mild Cognitive Impairment]], [[schizophrenia]], [[attention deficit disorder]], post-[[coronary bypass]] cognitive impairment, cognitive impairment associated with [[multiple sclerosis]], and [[Down syndrome]]. A 3 year NIH trial in patients with mild cognitive impairment reported that 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 analyses, a subgroup of individuals with the [[Apolipoprotein]] E4 genotype showed sustained benefits with donepezil throughout the study. However at this time donepezil is not indicated for prevention of dementia.
==Relationship to class and placebo==
Donepezil is generally better tolerated than others in its class, simpler to use, and the agent with the most number of well controlled clinical trials. Common side effects include [[bradycardia]], [[nausea]], [[diarrhea]], [[anorexia]], [[abdominal pain]], and vivid dreams. In 2006, Eisai, the manufacturer issued a statement that a single vascular dementia study found a difference in the percent of study participants who died in the donepezil group (1.7%) versus the placebo group (0%) and that this could be due to an unusually low death rate on the placebo group. An analysis of all three Vascular Dementia trials, according to Eisai, "shows no statistically significant differences in observed mortality rates between the donepezil and placebo groups (1.7% vs. 1.1%)". A physician has reported several cases of mania.<ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1189062 Mania associated with donepezil.]</ref>
==Use in the general population==
In July 2002, a pilot study, reported that donepezil improves the memory of aging pilots. The researchers trained pilots in a flight simulator to perform specific maneuvers and to respond to emergencies that developed during their mock flight, after giving half the pilots donepezil and half a [[placebo]]. One month later they retested the pilots and found that those who had taken the donepezil remembered their training better, as shown by improved performance.<ref>{{cite journal |author=Yesavage JA, Mumenthaler MS, Taylor JL, ''et al'' |title=Donepezil and flight simulator performance: effects on retention of complex skills |journal=Neurology |volume=59 |issue=1 |pages=123–5 |year=2002 |pmid=12105320 |doi=}}</ref> However, several other studies in normal older adults (before and after the above study) have not shown any significant cognitive improvements or shown inconsistent findings.{{fact|date=September 2007}}
==References==
<references/>
*Brenner, G. M. (2000). ''Pharmacology.'' Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6
*Canadian Pharmacists Association (2000). Compendium of Pharmaceuticals and Specialties (25th ed.). Toronto, ON: Webcom. ISBN 0-919115-76-4
== External links ==
* Official Aricept product site [http://www.aricept.com]
* Aricept entry at Drugs.com [http://www.drugs.com/aricept.html]
{{Anticholinesterases}}
{{Anti-dementia drugs}}
[[Category:Anticholinesterases]]
[[Category:Antidementia agents]]
[[Category:Alzheimer's disease]]
[[de:Donepezil]]
[[ja:塩酸ドネペジル]]
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