Although occurrence of seizures is rare, people who have a predisposition to seizures should be treated with caution.If daily donepezil has suspended for 7 days or less, restarting at the same dose is recommended, while if the suspension lasts longer than 7 days, retitrate from 5 mg daily is suggested. Mechanism of action
Donepezil binds and reversibly inactivates the cholinesterases, thus inhibiting hydrolysis of acetylcholine. This increases acetylcholine concentrations at cholinergic synapses.The precise mechanism of action of donepezil in patients with Alzheimers disease is not fully understood. Certainly, Alzheimers disease involves a substantial loss of the elements of the cholinergic system and it is generally accepted that the symptoms of Alzheimers disease are related to this cholinergic deficit, particularly in the cerebral cortex and other areas of the brain.In addition to its actions as an acetylcholinesterase inhibitor, donepezil has been found to act as a potent agonist of the σ1 receptor (Ki = 14.6 nM), and has been shown to produce specific antiamnestic effects in animals mainly via this action.Some noncholinergic mechanisms have also been proposed. Donepezil upregulates the nicotinic receptors in the cortical neurons, adding to neuroprotective property. It inhibits voltage-activated sodium currents reversibly and delays rectifier potassium currents and fast transient potassium currents, although this action is unlikely to contribute to clinical effects. Synergy
Donepezil was claimed to act synergistically with an agent called FK962 [283167-06-6] & FK960 [133920-70-4]. {potential activation of somatostatinergic neurotransmission}

Stereochemistry
Donepezil medications are racemates.
Other
Lewy body dementia: Some studies have shown benefits of donepezil for the treatment of cognitive and behavioral symptoms in Lewy body dementia. Traumatic brain injury: Some research suggests an improvement in memory dysfunction in patients with traumatic brain injury with donepezil use. Vascular dementia: Studies have shown that donepezil may improve cognition in patients with vascular dementia but not overall global functioning. Dementia associated with Parkinson disease: Some evidence suggests that donepezil can improve cognition, executive function, and global status in Parkinson disease dementia. Adverse effects
In clinical trials the most common adverse events leading to discontinuation were nausea, diarrhea, and vomiting. Other side effects included difficulty sleeping, muscle cramps and loss of appetite. Most side effects were observed in patients taking the 23 mg dose compared to 10 mg or lower doses. Side effects are mild and transient in most patients, lasting up to three weeks and usually improved even with continued use.Donepezil, like other cholinesterase inhibitors, 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. Precautions
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 with caution because increased risk of gastrointestinal bleeding was noted. Slow heart beat and fainting in people with heart problems were also seen. These symptoms may appear more frequent when initiating treatment or increasing the donepezil dose.