Acetylcholinesterase inhibitors cholinesterase inhibitor donepezil

FIGURE 12—24. Icon for the cholinesterase inhibitor donepezil. This is the current first-line treatment for Alzheimer s disease, since it is a once daily agent without significant hepatotoxicity. It is a reversible agent, selective for acetylcholinesterase (AChE) over butyrylcholinesterase (BuChE), developed by American and Japanese companies. 

There are no effective therapies for Alzheimer s disease and no cure. Treatment aims to enhance cholinergic transmission. The most useful drugs are central acetylcholinesterase inhibitors, for example donepezil. Acetylcholinesterase is the enzyme that normally breaks down acetylcholine after it has interacted with its receptors at the synapse. Inhibition of this enzyme in the brain increases the amount of acetylcholine available and prolongs its action. These drugs produce a modest improvement in memory or slow progression of symptoms in some patients. The response to anti-cholinesterase drugs may take several weeks. Their use is limited by side effects, which can be severe. 

Donepezil is a piperidine cholinesterase inhibitor, which reversibly and non-competitively inhibits centrally active acetylcholinesterase 34 This specificity is claimed to result in fewer peripheral side effects as compared to the other ChE inhibitors. 

Donepezil was the second cholinesterase inhibitor approved in the US [6]. It is currently the only acetylchohnesterase approved by the FDA for the treatment of severe Alzheimer s disease. Donepezil is a reversible, noncompetitive chohnesterase inhibitor. It has a high binding specificity for brain acetylcholinesterase, with httle to no affinity for butylchohnesterase. Compared with the other cholinesterase inhibitors in this class, donepezil may be better tolerated, with less gastrointestinal side effects. The long half-life of this medication allows once a day dosing (See Table 3). 

Donepezil is a cholinesterase inhibitor which increases acetylcholine by inhibiting acetylcholinesterase, thereby increasing cholinergic function. It is indicated in the treatment of mild to moderate dementia of the Alzheimer type. A deficiency of intact cholinergic neurons, particularly those extending from subcortical areas such as the nucleus basalis of Meynert, has been observed in patients with... 

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