Which of the following best characterises the mechanism of action of memantine in Alzheimer's Disease?

• A Reversible inhibition of acetylcholinesterase in cortical synapses
• B Uncompetitive, voltage-dependent NMDA receptor antagonism that blocks pathological glutamate excitotoxicity while preserving physiological NMDA activity ✓
• C Beta-amyloid aggregation inhibitor preventing plaque formation
• D Selective serotonin reuptake inhibition reducing neuroinflammation

Explanation

Memantine is an uncompetitive, voltage-dependent (open channel) antagonist of NMDA glutamate receptors. In Alzheimer's disease, sustained low-level glutamate release causes chronic partial NMDA receptor activation (background noise), which impairs synaptic signalling and contributes to excitotoxic neuronal damage. Memantine preferentially blocks tonically activated NMDA channels (pathological), displaces at high glutamate concentrations (normal synaptic transmission), thereby reducing excitotoxic damage while preserving physiological phasic NMDA signalling required for learning and memory. It is approved for moderate-to-severe AD.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.