Description

Donepezil, typically formulated as Donepezil Hydrochloride, is a medication belonging to the cholinesterase inhibitor class. It is a parasympathomimetic or cholinergic agent used for the symptomatic treatment of Alzheimer’s disease. Unlike some other drugs in its class, donepezil is a selective and reversible inhibitor of the enzyme acetylcholinesterase, and it has a long half-life, which allows for once-daily dosing. It is available in oral tablets, orally disintegrating tablets, and oral solution.

Indications

Donepezil is indicated for the treatment of mild, moderate, and severe dementia of the Alzheimer’s type. It does not cure the disease or halt its progression, but it can help to manage the cognitive and functional symptoms associated with it.

Mechanism of Action

Donepezil’s therapeutic effect is based on its ability to enhance the cholinergic system in the brain, which is deficient in patients with Alzheimer’s disease.

1. The Cholinergic System: Acetylcholine is a key neurotransmitter that plays a crucial role in cognitive functions such as memory, learning, attention, and executive function. In Alzheimer’s disease, the degeneration of cholinergic neurons leads to a significant reduction in acetylcholine levels in the brain.

2. Enzyme Inhibition: After acetylcholine is released into the synaptic cleft (the space between two neurons), its signal is terminated by an enzyme called acetylcholinesterase (AChE), which rapidly breaks down the acetylcholine molecule. Donepezil works by acting as a selective and reversible inhibitor of acetylcholinesterase.

3. Resulting Effect: By blocking the action of AChE, donepezil prevents the breakdown of acetylcholine. This leads to an increase in the concentration of acetylcholine in the synaptic cleft, allowing the neurotransmitter to bind more frequently and for a longer duration to its receptors on the postsynaptic neuron. This enhances cholinergic neurotransmission.

By increasing the amount of available acetylcholine, donepezil helps to compensate for the deficiency and can lead to modest improvements in a patient’s memory, cognitive function, and ability to perform daily activities. Its selectivity for AChE over other cholinesterase enzymes, such as butyrylcholinesterase, is a key feature of its pharmacological profile.