Memantine mechanism — MRCPsych Paper A MCQ

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EasyPsychopharmacologyMemantine mechanismMRCPsych Paper A

An 82-year-old woman with moderate Alzheimer disease cannot tolerate an acetylcholinesterase inhibitor because of bradycardia and syncope. Memantine is considered. What is its principal mechanism of action?

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Correct answer: A — Uncompetitive antagonism at NMDA receptors

Memantine is a voltage-dependent, moderate-affinity, uncompetitive antagonist at N-methyl-D-aspartate (NMDA) receptors. It modulates excessive glutamatergic NMDA-receptor activity while allowing more physiological neurotransmission. NICE recommends memantine monotherapy in moderate Alzheimer disease when acetylcholinesterase inhibitors are contraindicated or not tolerated, as in this patient. Option B describes donepezil, rivastigmine and galantamine, which can exacerbate bradycardia and syncope. Irreversible monoamine oxidase-B inhibition is associated with drugs such as selegiline and rasagiline, not memantine. Dopamine D4-receptor antagonism and nicotinic receptor agonism are not mechanisms of memantine.

Reference: Electronic Medicines Compendium, Memantine 20 mg film-coated tablets, Summary of Product Characteristics, section 5.1 Pharmacodynamic properties, updated 8 January 2024. https://www.medicines.org.uk/emc/product/14496/smpc