Trade names Aricept, Adlarity.
Donepezil hydrochloride
Pregnancy category AU: B3
Routes of administration By mouth, transdermal
Drug class Acetylcholinesterase inhibitor
Bioavailability 100%
Protein binding 96%, albumin (about 75%) and alpha1-acid glycoprotein (21%).
Metabolism CYP2D6, CYP3A4, and glucuronidation.
Four major metabolites, two of which are active.
Onset of action Peak plasma levels in 3–4 h.
Elimination half-life 70 hours.
Around 100 hours in elderly patients.
Duration of action ; With daily dosing, steady-state concentration is reached in 15–21 days.
Excretion mostly by the kidneys.
Around 17% is excreted unchanged in the urine.
About 15% to 20% is excreted in feces.
Donepezil, sold under the brand name Aricept among others, is a medication used to treat dementia of the Alzheimer’s type.
It use results in a small benefit in mental function and ability to function.
It has not been shown to change the progression of the disease.
Treatment should be stopped if no benefit is seen.
It is taken by mouth or via a transdermal patch.
Common side effects include nausea, trouble sleeping, aggression, diarrhea, feeling tired, and muscle cramps.
Serious side effects may include abnormal heart rhythms, urinary incontinence, and seizures.
Donepezil is a centrally acting reversible acetylcholinesterase inhibitor.
It is structurally unrelated to other anticholinesterase agents.
No evidence that donepezil or other similar agents alter the course or progression of Alzheimer’s disease.
Six-to-twelve-month controlled studies have shown modest benefits in cognition or behavior.
Some studies have shown benefits of donepezil for the treatment of cognitive and behavioral symptoms in Lewy body dementia.
Traumatic brain injury is associated with an improvement in memory dysfunction with donepezil use.
Vascular dementia: Studies have shown that donepezil may improve cognition in patients with vascular dementia but not overall global functioning.
Some evidence suggests that donepezil can improve cognition, executive function, and global status in Parkinson disease dementia.
The most common adverse events leading to discontinuation were nausea, diarrhea, and vomiting, and other side effects included difficulty sleeping, muscle cramps and loss of appetite.
Side effects are mild and transient in most patients, lasting up to three weeks and usually improved even with continued use.
It can cause nightmares due to enhanced activation of the visual association cortex during REM sleep.
Dosing donepezil in the morning can reduce the frequency of nightmares.
Donepezil should be used with caution in people with heart disease, cardiac conduction disturbances, chronic obstructive pulmonary disease, asthma, severe cardiac arrhythmia and sick sinus syndrome.
People with peptic ulcer disease or taking NSAIDs should use donepezl with caution because increased risk of gastrointestinal bleeding was noted.
Slow heart beat and fainting in people with heart problems were also seen.
Although occurrence of seizures is rare, people who have a predisposition to seizures should be treated with caution.[3]
Donepezil binds and reversibly inhibits enzymes called cholinesterases, especially acetylcholinesterase, thus inhibiting hydrolysis of acetylcholine.
This increases acetylcholine concentrations at cholinergic synapses.
Alzheimer’s disease involves a substantial loss of the elements of the cholinergic system and it is generally accepted that the symptoms of Alzheimer’s disease are related to this cholinergic deficit, particularly in the cerebral cortex and other areas of the brain.
Donepezil upregulates the nicotinic receptors in the cortical neurons, resulting in neuroprotective activity.
Donepezil has been used in other cognitive disorders, including Lewy body dementia, and vascular dementia, but it is not currently approved for these indications.
It has has been found to improves sleep apnea and gait in people with mild Alzheimer’s.
Donepezil has also been studied in people with mild cognitive impairment, schizophrenia, attention deficit disorder, post-coronary artery bypass surgery cognitive impairment, cognitive impairment associated with multiple sclerosis, and Down syndrome.
National Institutes of Health trial in people 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.
A secondary analysis, a subgroup of individuals with the apolipoprotein E4 genotype showed sustained benefits throughout the study.
At this time, though, donepezil is not indicated for prevention of dementia.
Donepezil has shown mixed results for improving cognitive abilities in healthy adult individuals.
A placebo controlled study investigating donepezil’s effects across a variety of memory tests reported an improvement in spatial memory accuracy both before and after dosing.
However, a placebo controlled experiments evaluating donepezil’s effects in older but healthy subjects reported impairment after acute (5 hours after dose) and chronic (4 weeks) donepezil administration.
With Tourette syndrome and ADHD, donepezil may reduce tics while it had no effect on ADHD’s symptoms.
Donepezil, along with other cholinesterase inhibitors, may having potential for trouble behaviors: irritability, hyperactivity, and difficulty in social communication which are typically seen in those with pervasive developmental disorder, pervasive developmental disorder not otherwise specified, and autism-spectrum disorder.
A subset of patients suffering from restrictive anorexia nervosa have enhanced habit formation compared with healthy controls, the effects of donepezil and other drugs that act as cholinesterase inhibitors could thus be effective in the treatment of the disorder: However, no trial to date supports this hypothesis.