Definition

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. [HMDB]

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. Donepezil is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. If this proposed mechanism of action is correct, donepezil's effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. 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, schizophrenia, attention deficit disorder, post-coronary bypass cognitive impairment, cognitive impairment associated with multiple sclerosis, and Down syndrome.

General Information

Mechanism of Action