Mechanism of action of memantine

Curr Opin Pharmacol. 2006 Feb;6(1):61-7. doi: 10.1016/j.coph.2005.09.007. Epub 2005 Dec 20.


Memantine is a clinically useful drug in many neurological disorders, including Alzheimer's disease. The principal mechanism of action of memantine is believed to be the blockade of current flow through channels of N-methyl-d-aspartate (NMDA) receptors--a glutamate receptor subfamily broadly involved in brain function. Surprisingly, other drugs that block NMDA receptor channels, such as ketamine, exhibit serious deleterious effects. The unusual therapeutic utility of memantine probably results from inhibitory mechanisms shared with ketamine, combined with actions specific to memantine. These potentially important differences between memantine and ketamine include effects on gating of blocked channels and binding of memantine to two sites on NMDA receptors. Because modulation of NMDA receptor activity can increase or decrease excitability of neuronal circuits, subtle differences in the mechanisms of action of NMDA receptor antagonists can strongly impact on their clinical effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Humans
  • Ion Channel Gating
  • Ketamine / pharmacology
  • Magnesium / metabolism
  • Memantine / pharmacology*
  • Memantine / therapeutic use
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / metabolism


  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine
  • Magnesium
  • Memantine