Aricept

アリセプト

関

donepezil、donepezil hydrochloride

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/03/27 15:47:31」(JST)

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Donepezil

Systematic (IUPAC) name
(RS)-2-[(1-benzyl-4-piperidyl)methyl]- 5,6-dimethoxy-2,3-dihydroinden-1-one
Clinical data
Trade names	Aricept
AHFS/Drugs.com	monograph
MedlinePlus	a697032
Pregnancy cat.	C
Legal status	℞ Prescription only
Routes	Oral tablet, 5,10 & 23mg
Pharmacokinetic data
Bioavailability	100 (%)
Protein binding	96%
Half-life	70 hours
Excretion	0,11-0,13 (l/h/kg)
Identifiers
CAS number	120014-06-4 Y
ATC code	N06DA02
PubChem	CID 3152
DrugBank	DB00843
ChemSpider	3040 Y
UNII	8SSC91326P Y
KEGG	D07869 Y
ChEBI	CHEBI:53289 Y
ChEMBL	CHEMBL502 Y
Chemical data
Formula	C24H29NO3
Mol. mass	379.492 g/mol
SMILES O=C2c1cc(OC)c(OC)cc1CC2CC4CCN(Cc3ccccc3)CC4
InChI InChI=1S/C24H29NO3/c1-27-22-14-19-13-20(24(26)21(19)15-23(22)28-2)12-17-8-10-25(11-9-17)16-18-6-4-3-5-7-18/h3-7,14-15,17,20H,8-13,16H2,1-2H3 Y Key:ADEBPBSSDYVVLD-UHFFFAOYSA-N Y
Y (what is this?)  (verify)

Donepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the palliative treatment of mild to moderate 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 half-life of about 70 hours, it can be taken once a day.

Medical uses

Donepezil inhibiting Torpedo californica acetylcholinesterase. See Proteopedia 1eve.

Alzheimer's disease

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. Pilot studies have reported 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 Clinical Excellence (NICE) withdrew its recommendation for use of the drug for mild-to-moderate AD, on the basis of no significant improvement in functional outcome, quality of life, or behavioral symptoms. However, NICE revised its guidelines to suggest donepezil be used in moderate-stage patients for whom the evidence is strongest.

While the drug is currently indicated for mild to moderate Alzheimer's, evidence from two clinical trials also indicates 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 donepezil improves cognitive function even in patients with severe AD symptoms.

Dosage

10mg Aricept pill

In mild to moderate Alzheimer’s Disease, a starting dose of 5 mg given once daily should be used. In a minimum of four to six weeks, an increase to 10 mg is recommended. The usual dose is 5 to 10 mg once daily. Moderate to severe AD indicates the same regimen, but in a minimum of three months, a patient may receive a dose of 23 mg once daily. Dementia patients should receive 5–10 mg once daily. The maximum daily dose is 23 mg once daily. Clinicians should use caution in prescribing the maximum daily dose as the risk of severe side effects may outweigh the unclear clinical benefits. In the UK, the maximum licensed dose is 10 mg.

Contraindications

Donepezil (Aricept) should be used with caution in patient 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. The British Medical Journal (BMJ) cautioned that the largest dosage, 23 mg, was crafted to extend patent protection rather than for medical reasons, and was not shown to be more effective compared to the 10 mg dose.

Other

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.

Donepezil has also been studied in patients with mild cognitive impairment, schizophrenia, attention deficit disorder, postcoronary bypass 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 (Petersen 2005). At this time, though, donepezil is not indicated for prevention of dementia.

Recent studies suggest donepezil can improve speech in children with autism. The studies found the speech of autistic children who were mildly to moderately affected appeared to improve from the use of donepezil.

Adverse effects

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 percentage of study participants who died in the donepezil group (1.7%) versus the placebo group (0%), and 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." A physician has reported several cases of mania.

Development and marketing

Research leading to the development of donepezil began in 1983 at Eisai, and the first Phase I clinical trial took place in 1989. 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.

Combinations

References

External links

• 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
• http://www.websciences.org/cftemplate/NAPS/archives/indiv.cfm?ID=20081395
• 3D Molecular structure of Donepezil
• Donepezil bound to proteins in the PDB

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 認知症治療におけるコリンエステラーゼ阻害剤 cholinesterase inhibitors in the treatment of dementia
• 2. 大脳皮質基底核変性症 corticobasal degeneration
• 3. 高齢者の双極性障害：急性治療 geriatric bipolar disorder acute treatment
• 4. 離人症性障害の治療 treatment of depersonalization disorder
• 5. 認知症の治療 treatment of dementia

English Journal

• Conformational analysis and parallel QM/MM X-ray refinement of protein bound anti-Alzheimer drug donepezil.

• Fu Z, Li X, Miao Y, Merz KM Jr.SourceDepartment of Chemistry and the Quantum Theory Project, 2328 New Physics Building, P.O. Box 118435, University of Florida, Gainesville, Florida, 32611-8435.
• Journal of chemical theory and computation.J Chem Theory Comput.2013 Dec 3;9(3):1686-1693. Epub 2013 Feb 18.
• The recognition and association of donepezil with acetylcholinesterase (AChE) has been extensively studied in the past several decades because of the former's use as a palliative treatment for mild Alzheimer disease. Herein we examine the conformational properties of donepezil and we re-examine the
• PMID 23526889

• Concentration of donepezil to the cognitive response in Alzheimer disease.

• Yang YH, Chen CH, Chou MC, Li CH, Liu CK, Chen SH.SourceFrom the *Department of and Master's Program in Neurology, Faculty of Medicine; †Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University; ‡Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital; §Department of Neurology Kaohsiung Municipal Hsiaokang Hospital; ∥Graduate Institute of Pharmaceutical Sciences, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
• Journal of clinical psychopharmacology.J Clin Psychopharmacol.2013 Jun;33(3):351-5. doi: 10.1097/JCP.0b013e31828b5087.
• BACKGROUND: Donepezil has been approved, and higher dosages are recommended for the treatment of Alzheimer disease (AD). However, a few studies have reported different cognitive responses in patients with AD treated with donepezil without measuring the concentration.METHODS: We evaluated the relatio
• PMID 23609381

Japanese Journal

• アルツハイマー型認知症患者に対するドネペジル塩酸塩の長期投与による病態の推移および安全性 : 長期・大規模調査「J-GOLD」の中間集計結果

• 新井 平伊,秋山 弘之,兼松 徹 [他]
• 老年精神医学雑誌 24(11), 1160-1169, 2013-11
• NAID 40019896250

• アリセプト内服ゼリーの開発

• 原田 努,櫻井 真帆,安岡 光一 [他]
• 製剤機械技術学会誌 = Journal of pharmaceutical machinery and engineering 21(5), 557-563, 2012
• NAID 40019515285

• Preparation and Evaluation of Taste-Masked Donepezil Hydrochloride Orally Disintegrating Tablets

• Yan Yi-Dong,Woo Jong Soo,Kang Joon Heok [他],Yong Chul Soon,Choi Han-Gon
• Biological and Pharmaceutical Bulletin 33(8), 1364-1370, 2010
• … Dissolution in vitro and pharmacokinetics in rats were evaluated for the tested ODTs compared to the donepezil hydrochloride commercial product (ARICEPT®). … Both tablets showed comparable dissolution patterns in vitro and similar area under curve from 0 to 24 h (AUC0—24), Cmax and Tmax of DH in vivo to each other, suggesting that the tested ODTs might give the similar drug efficacy in rats compared to that of ARICEPT®. …
• NAID 130000300362

Related Links

• アルツハイマー型、レビー小体型認知症を支える【アリセプト ...

アリセプト www.aricept.jp 小 中 大 アルツハイマー型認知症のアリセプト ホーム サイトマップ 関連リンク 製品情報概要（PDF） 効能・効果追加のご案内（PDF） 診断基準 有効性・安全性（PDF） アリセプト服用指導箋（PDF） 認知機能 ...

• 医療関係者のみなさまへ ｜ アルツハイマー型認知症を支える ...

医療関係者のみなさまへ｜エーザイのアルツハイマー型認知症治療薬「アリセプト」のサイトです。アルツハイマー型認知症の患者様とそのご家族をフルステージ（初期・中等度・高度）で支え、コミュニケーションをサポートする ...

Related Pictures

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★リンクテーブル★

リンク元	「ドネペジル」「donepezil hydrochloride」

「ドネペジル」

　　[★]

英

donepezil

化

塩酸ドネペジル

商

アリセプト Aricept

関

アルツハイマー病。その他の中枢神経系用薬

• 抗認知症薬
• アルツハイマー型認知症の治療薬である。
• コリンエステラーゼ阻害薬。可逆的
• 血液脳関門を抜けて脳内でのアセチルコリン濃度を上昇させ、コリン作動性ニューロンの運動を活発にすることで、認知症の症状(認知症の中核症状)をを和らげる。症状を和らげるので対症療法である。

• 特徴

脳への移行が多い

末梢性副作用が少ない。(ドネペシルは偽性コリンエステラーゼの阻害が少ない)

肝毒性が少ない

血漿中濃度消失半減期が長く1日1回投与でよい。

• 副作用

• アセチルコリンエステラーゼの阻害作用によるコリン作動性作用に基づく。
• 消化器症状
• 循環器系症状：アセチルコリンエステラーゼの阻害作用による心臓刺激

• 慎重投与

• 1)洞不全症候群、心房内及び房室接合部伝導障害等の心疾患(迷走神経刺激作用により徐脈あるいは不整脈の可能性)
• 2)消化性潰瘍の既往歴、NSAIDs投与中(胃酸分泌の促進及び消化管運動の促進により消化性潰瘍を悪化の可能性)
• 3)気管支喘息又は閉塞性肺疾患の既往歴(気管支平滑筋の収縮及び気管支粘液分泌の亢進により症状悪化の可能性)
• 4)錐体外路障害(パーキンソン病、パーキンソン症候群等)(線条体のコリン系神経の亢進により症状誘発又は増悪の可能性)

→　既往歴のチェック、12誘導心電図、聴診、予防的PPI投与 (以上はエビデンスなし)

• 用量

• 錠剤：3mgから開始して、1-2週間後に5mgに増量する。症状に応じて5mgにしてから4週間以上空けて10mgまで増量できる。

「donepezil hydrochloride」

　　[★]

• 塩酸ドネペジル

関

Aricept、donepezil