Memantine, used in moderate-to-severe Alzheimer's disease, exerts its mechanism by:
- A Blocking NMDA glutamate receptors in a voltage-dependent, uncompetitive manner, reducing excitotoxic calcium influx ✓
- B Inhibiting butyrylcholinesterase in the cerebral cortex
- C Blocking amyloid-beta oligomers from binding to neuronal membrane receptors
- D Enhancing acetylcholine release via presynaptic nicotinic receptor potentiation
Correct answer: A. Blocking NMDA glutamate receptors in a voltage-dependent, uncompetitive manner, reducing excitotoxic calcium influx
Explanation
Memantine is an uncompetitive, low-affinity NMDA receptor antagonist with voltage-dependence. It blocks the pathologically elevated tonic activation of NMDA receptors by glutamate (excitotoxicity) while preserving the physiological phasic NMDA activation needed for learning and memory. This selective blockade reduces chronic calcium influx and neuronal death. Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) work via acetylcholinesterase (and butyrylcholinesterase for rivastigmine) inhibition; memantine has a completely different mechanism.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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