| Record Information |
|---|
| Version |
3.5 |
| Creation Date |
2006-10-17 05:44:46 -0600 |
| Update Date |
2013-02-08 17:13:50 -0700 |
| HMDB ID |
HMDB05041 |
| Secondary Accession Numbers |
None |
| Metabolite Identification |
|---|
| Common Name |
Donepezil |
| Description |
Donepezil, marketed under the trade name Aricept (Eisai), is a centrally acting reversible acetyl cholinesterase 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. Donepezil is a centrally acting reversible acetyl cholinesterase inhibitor. Its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine. It is well absorbed in the gut with 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. 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. 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 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; 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. 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 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. 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. 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. 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. |
| Structure |
Download:
MOL |
SDF |
SMILES |
InChI
Display:
2D Structure |
3D Structure
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| Synonyms |
- Aricept
- Aricept ODT
- Donepezil hydrochloride
|
| Chemical Formula |
C24H29NO3 |
| Average Molecular Weight |
379.492 |
| Monoisotopic Molecular Weight |
379.214743799 |
| IUPAC Name |
2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one |
| Traditional IUPAC Name |
donepezil |
| CAS Registry Number |
120014-06-4 |
| SMILES |
COC1=C(OC)C=C2C(=O)C(CC3CCN(CC4=CC=CC=C4)CC3)CC2=C1 |
| InChI Identifier |
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 |
| InChI Key |
ADEBPBSSDYVVLD-UHFFFAOYSA-N |
| Chemical Taxonomy |
|---|
| Kingdom |
Organic Compounds |
| Super Class |
Aromatic Heteropolycyclic Compounds |
| Class |
Indanes |
| Sub Class |
Indanones |
| Other Descriptors |
- Aromatic Heteropolycyclic Compounds
- Indanes
- cyclic ketone(ChEBI)
- piperidines(ChEBI)
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| Substituents |
- Alkyl Aryl Ether
- Anisole
- Ketone
- Phenylmethylamine
- Piperidine
- Tertiary Aliphatic Amine (Trialkylamine)
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| Direct Parent |
Indanones |
| Ontology |
|---|
| Status |
Expected and Not Quantified |
| Origin |
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| Biofunction |
Not Available |
| Application |
Not Available |
| Cellular locations |
Not Available |
| Physical Properties |
|---|
| State |
Solid |
| Experimental Properties |
| Property |
Value |
Reference |
| Melting Point |
Not Available |
Not Available |
| Boiling Point |
Not Available |
Not Available |
| Water Solubility |
Not Available |
Not Available |
| LogP |
Not Available |
Not Available |
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| Predicted Properties |
|
| Spectra |
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Not Available
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| Biological Properties |
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| Cellular Locations |
Not Available
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| Biofluid Locations |
Not Available
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| Tissue Location |
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| Pathways |
Not Available
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| Normal Concentrations |
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Not Available |
| Abnormal Concentrations |
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|
Not Available |
| Associated Disorders and Diseases |
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| Disease References |
None |
| Associated OMIM IDs |
None |
| External Links |
|---|
| DrugBank ID |
Not Available |
| Phenol Explorer Compound ID |
Not Available |
| Phenol Explorer Metabolite ID |
Not Available |
| FoodDB ID |
FDB023607 |
| KNApSAcK ID |
Not Available |
| Chemspider ID |
3040  |
| KEGG Compound ID |
Not Available |
| BioCyc ID |
Not Available |
| BiGG ID |
Not Available |
| Wikipedia Link |
Donepezil |
| NuGOwiki Link |
HMDB05041 |
| Metagene Link |
HMDB05041 |
| METLIN ID |
Not Available |
| PubChem Compound |
3152 |
| PDB ID |
Not Available |
| ChEBI ID |
53289 |
| References |
|---|
| Synthesis Reference |
Sugimoto, Hachiro; Tsuchiya, Yutaka; Higurashi, Kunizou; Karibe, Norio; Iimura, Yuoichi; Sasaki, Atsushi; Yamanashi, Yoshiharu; Ogura, Hiroo; Araki, Shin; et al. Preparation of 1-benzyl-4-(substituted alkyl)piperidines and analogs as acetylcholinesterase inhibitors. Eur. Pat. Appl. (1988), 103 pp. CODEN: EPXXDW EP 296560 A2 19881228 CAN 110:173102 AN 1989:173102 |
| Material Safety Data Sheet (MSDS) |
Not Available
|
| General References |
- Wang LN, Wang W, Zhang XH, Ma L, Yin H, Li DJ: [An interventional study on amnestic mild cognitive impairment with small dose donepezil] Zhonghua Nei Ke Za Zhi. 2004 Oct;43(10):760-3.
Pubmed: 15631830
- Emre M: Switching cholinesterase inhibitors in patients with Alzheimer's disease. Int J Clin Pract Suppl. 2002 Jun;(127):64-72.
Pubmed: 12139369
- Nakano S, Asada T, Matsuda H, Uno M, Takasaki M: Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer's disease. J Nucl Med. 2001 Oct;42(10):1441-5.
Pubmed: 11585854
- Hayslett RL, Tizabi Y: Effects of donepezil, nicotine and haloperidol on the central serotonergic system in mice: implications for Tourette's syndrome. Pharmacol Biochem Behav. 2005 Aug;81(4):879-86.
Pubmed: 16045972
- Wilkinson DG, Francis PT, Schwam E, Payne-Parrish J: Cholinesterase inhibitors used in the treatment of Alzheimer's disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging. 2004;21(7):453-78.
Pubmed: 15132713
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