Repositioning Candidate Details
| Candidate ID: | R0305 |
| Source ID: | DB00843 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Donepezil |
| Synonyms: | Domepezil |
| Molecular Formula: | C24H29NO3 |
| SMILES: | COC1=C(OC)C=C2C(=O)C(CC3CCN(CC4=CC=CC=C4)CC3)CC2=C1 |
| Structure: |
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| DrugBank Description: | In 2016, the global burden of dementia was estimated to be 43.8 million, demonstrating a significant increase from a global prevalence of 20.2 million in 1990. Donepezil, also known as Aricept, is a piperidine derivative acetylcholinesterase inhibitor used in the management of the dementia of Alzheimer's Disease, and in some cases, is used to manage other types of dementia. Donepezil was first approved by the FDA in 1996, and its extended-release form was approved in combination with in 2014 to manage moderate and severe forms of Alzheimer's dementia. Though it does not alter the progression of Alzheimer's disease, donepezil is effective in managing the symptoms of its associated dementia. |
| CAS Number: | 120014-06-4 |
| Molecular Weight: | 379.492 |
| DrugBank Indication: | Donepezil is indicated for the management of mild to moderate Alzheimer’s Disease at doses of 5 mg or 10 mg. It is also indicated for the management of moderate to severe Alzheimer’s Disease in a higher dose of 10 mg or 23 mg administered once daily. Off-label uses include the management of vascular dementia, Parkinson's Disease-associated dementia, and Lewy body dementia, among others. When combined with memantine, the extended-release form of donepezil is indicated to treat the symptoms of moderate to severe dementia. |
| DrugBank Pharmacology: | By inhibiting the acetylcholinesterase enzyme, donepezil improves the cognitive and behavioral signs and symptoms of Alzheimer's Disease, which may include apathy, aggression, confusion, and psychosis. |
| DrugBank MoA: | The commonly accepted cholinergic hypothesis proposes that a portion of the cognitive and behavioral decline associated with Alzheimer's are the result of decreased cholinergic transmission in the central nervous system. Donepezil selectively and reversibly inhibits the acetylcholinesterase enzyme, which normally breaks down acetylcholine. The main pharmacological actions of this drug are believed to occur as the result of this enzyme inhibition, enhancing cholinergic transmission, which relieves the symptoms of Alzheimer's dementia. In addition to the above, other mechanisms of action of donepezil are possible, including the opposition of glutamate-induced excitatory transmission via downregulation of NMDA receptors and the regulation of amyloid proteins, which have demonstrated significant effects on the disease process of Alzheimer's. Other possible targets for donepezil may also include the inhibition various inflammatory signaling pathways, exerting neuroprotective effects. |
| Targets: | Acetylcholinesterase inhibitor; 5-hydroxytryptamine receptor 2A inducer; Cholinesterase inducer; Nitric oxide synthase, brain inhibitor&inducer; Tumor necrosis factor-inducible gene 6 protein inhibitor; Interleukin-1 beta inhibitor&inducer; Nuclear factor NF-kappa-B inhibitor; NMDA receptor downregulator |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
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