Cholinesterase inhibition — MRCPsych Paper A MCQ

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HardNeurophysiology and neurochemistryCholinesterase inhibitionMRCPsych Paper A

A 78-year-old woman with mild Alzheimer disease is prescribed a once-daily piperidine cognitive enhancer. It reversibly inhibits the predominant cholinesterase in the brain and is more than 1000-fold more potent against this target than against butyrylcholinesterase in vitro. Which enzyme is its principal target?

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Correct answer: B — Acetylcholinesterase

The correct answer is acetylcholinesterase. The piperidine derivative described is donepezil, a specific, reversible acetylcholinesterase inhibitor. Inhibiting this enzyme reduces acetylcholine hydrolysis and thereby increases cholinergic neurotransmission; the licensed product information states that donepezil is over 1000-fold more potent against acetylcholinesterase than butyrylcholinesterase in vitro. Butyrylcholinesterase is therefore a much weaker target. Choline acetyltransferase synthesises acetylcholine rather than terminating its action. Monoamine oxidase B and catechol-O-methyltransferase metabolise monoamines and are principally relevant to dopaminergic pharmacology, including treatments for Parkinson disease, rather than the cholinergic action of donepezil.

Reference: Electronic Medicines Compendium, Aricept Tablets 5 mg Summary of Product Characteristics, section 5.1 Pharmacodynamic properties, revised 2022. https://www.medicines.org.uk/emc/product/3776/smpc