Human Metabolome Database Version 3.5

Showing metabocard for Donepezil (HMDB05041)

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 Thumb
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Synonyms
  1. Aricept
  2. Aricept ODT
  3. 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)
Substituents
  • Alkyl Aryl Ether
  • Anisole
  • Ketone
  • Phenylmethylamine
  • Piperidine
  • Tertiary Aliphatic Amine (Trialkylamine)
Direct Parent Indanones
Ontology
Status Expected and Not Quantified
Origin
  • Endogenous
Biofunction Not Available
Application Not Available
Cellular locations
  • Membrane (predicted from logP)
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
Predicted Properties
Property Value Source
Water Solubility 0.0045 g/L ALOGPS
LogP 4.14 ALOGPS
LogP 4.21 ChemAxon
LogS -4.93 ALOGPS
pKa (strongest acidic) 17.02 ChemAxon
pKa (strongest basic) 8.62 ChemAxon
Hydrogen Acceptor Count 4 ChemAxon
Hydrogen Donor Count 0 ChemAxon
Polar Surface Area 38.77 A2 ChemAxon
Rotatable Bond Count 6 ChemAxon
Refractivity 112.11 ChemAxon
Polarizability 44.26 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge 1 ChemAxon
Spectra
Not Available
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biofluid Locations Not Available
Tissue Location
  • Brain
Pathways Not Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease References None
Associated OMIM IDs None
DrugBank ID Not Available
DrugBank Metabolite 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 Link_out
KEGG Compound ID Not Available
BioCyc ID Not Available
BiGG ID Not Available
Wikipedia Link Donepezil Link_out
NuGOwiki Link HMDB05041 Link_out
Metagene Link HMDB05041 Link_out
METLIN ID Not Available
PubChem Compound 3152 Link_out
PDB ID Not Available
ChEBI ID 53289 Link_out
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
  1. 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 Link_out
  2. Emre M: Switching cholinesterase inhibitors in patients with Alzheimer's disease. Int J Clin Pract Suppl. 2002 Jun;(127):64-72. Pubmed: 12139369 Link_out
  3. 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 Link_out
  4. 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 Link_out
  5. 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 Link_out

Enzymes
Name: Acetylcholinesterase
Reactions: Not Available
Gene Name: ACHE
Uniprot ID: P22303 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Cholinesterase
Reactions: Not Available
Gene Name: BCHE
Uniprot ID: P06276 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Cytochrome P450 3A4
Reactions: Not Available
Gene Name: CYP3A4
Uniprot ID: P08684 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Cytochrome P450 2D6
Reactions: Not Available
Gene Name: CYP2D6
Uniprot ID: P10635 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: 5-hydroxytryptamine receptor 2A
Reactions: Not Available
Gene Name: HTR2A
Uniprot ID: P28223 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA