Donepezil — Acetylcholinesterase Inhibitor
Donepezil is a reversible inhibitor of the enzyme acetylcholinesterase, primarily used to treat cognitive symptoms in Alzheimer's disease. In the context of longevity, it is of interest for its potential to maintain cognitive function and delay the progression of neurodegenerative decline by enhancing cholinergic neurotransmission.
Mechanism of Action
Donepezil reversibly and non-competitively inhibits centrally-active acetylcholinesterase, the enzyme responsible for the hydrolysis of acetylcholine. By preventing the breakdown of acetylcholine, it increases the concentration and duration of action of this neurotransmitter at synapses in the central nervous system. This enhanced cholinergic signaling supports memory, attention, and learning processes. While it does not alter the underlying pathology of Alzheimer's disease, such as amyloid-beta plaque formation, it provides symptomatic relief and may exert mild neuroprotective effects through the modulation of neuroinflammation.
Human Trial Evidence
Donepezil is FDA-approved and has been extensively studied in human clinical trials for mild, moderate, and severe Alzheimer's disease, showing consistent improvements in cognitive scores. However, there are no published human longevity trials evaluating its use for lifespan extension or cognitive enhancement in healthy, non-demented aging populations.
Dosing Protocol
The standard starting dose is 5 mg once daily, typically taken in the evening. After 4 to 6 weeks, the dose may be increased to 10 mg once daily. Donepezil is a prescription-only medication.
Safety & Contraindications
Common adverse effects include nausea, diarrhea, vomiting, insomnia, and muscle cramps. It is contraindicated in patients with known hypersensitivity to donepezil. Caution is advised in patients with sick sinus syndrome, severe asthma, or a history of peptic ulcer disease due to increased vagal tone.