NMDA Receptor Antagonists
NMDA receptor antagonists are drugs that inhibit the NMDA receptor and lower its signaling. The main drug in this category is memantine, which is used for moderate to severe Alzheimer’s disease. In the broader neurodegeneration landscape, it belongs to the group of symptom-managing cognitive drugs, not disease-modifying therapies.
Biological Rationale
Excessive glutamatergic (excitatory) signaling through NMDA receptors has been proposed to contribute to toxic stress and Alzheimer’s symptoms. Memantine acts as a low-to-moderate affinity uncompetitive NMDA receptor antagonist, aiming to reduce pathological signaling while preserving more normal neurotransmission.
Evidence Strength
Strong
It is an established symptomatic treatment, used alone or with a cholinesterase inhibitor. But the evidence does not support it as a treatment that prevents or slows the core neurodegenerative process.
Limitations
The benefits are generally modest, and there is no evidence that memantine prevents or slows neurodegeneration itself. Memantine is generally well tolerated, but possible side effects include dizziness, headache, confusion, constipation, and, less commonly, changes in blood pressure or mood.
Sources
- McShane, R., Westby, M. J., Roberts, E., et al. (2019). Memantine for dementia.
- U.S. Food and Drug Administration. NAMENDA® (memantine hydrochloride) tablets, prescribing information.
- Tari, P. K., et al. (2024). Memantine: Updating a rare success story in pro-cognitive therapeutics.