In Alzheimer's disease, memantine acts on which receptor system, and in which cognitive domain does it have the strongest evidence for benefit compared with AChEIs?
- A AMPA receptor potentiation; attention and processing speed
- B Nicotinic acetylcholine receptor agonism; episodic memory
- C mGluR5 negative allosteric modulation; language
- D NMDA receptor uncompetitive antagonism; moderate-to-severe Alzheimer's — activities of daily living and global functioning ✓
Explanation
Memantine is an uncompetitive, low-affinity NMDA receptor antagonist that blocks pathological tonic NMDA receptor activation by glutamate (excitotoxicity) while preserving physiological phasic activation required for learning and memory. Its FDA approval is specifically for moderate-to-severe Alzheimer's disease (MMSE 3–14), and evidence supports benefits in functional ability (ADLs) and global clinical measures. Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) are approved for mild-to-severe AD. Combination of memantine + AChEI is used in moderate-to-severe stages; the combination has additive but modest benefits.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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