Memantine (Namenda)

Mechanism of action

Uncompetitive NMDA receptor antagonist — blocks the NMDA channel only when it's pathologically over-activated, sparing normal signaling. The voltage-dependent block dissociates rapidly during physiological depolarization but remains during prolonged pathological activation. This mechanism reduces glutamate excitotoxicity without producing the cognitive impairment of stronger NMDA antagonists.

History

Memantine was originally developed by Eli Lilly in the 1960s as an anti-influenza drug. Its NMDA antagonist activity was identified later. Merz Pharmaceuticals developed it for Alzheimer's disease in the 1980s-1990s; FDA approval came in 2003 for moderate-to-severe disease. The combined memantine + cholinesterase inhibitor regimen is the standard for moderate-to-severe Alzheimer's. McShane 2019 Cochrane review supports efficacy.

Benefits

• Cognitive and functional decline in moderate-to-severe Alzheimer's

  EVIDENCEA

  McShane 2019 Cochrane.

• Combined with donepezil for additive benefit

  EVIDENCEA

  Multiple trials.

Side effects

• Dizzinesscommonmild
• Headachecommonmild
• Confusionuncommonmoderate

Cited research

• Memantine for dementia: Cochrane review (McShane)2019
  PMID 30891742 ↗
• Memantine + donepezil combination therapy (Tariot)2004
  PMID 14722150 ↗
• Memantine NMDA antagonist mechanism (Lipton)2006
  PMID 16877800 ↗

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