Even thoughtThe FDA rejected the expansion of Namenda for the treatment of mild AD in 2005 it has become more widely prescribed and has come to be the 2nd wave treatment, following, and often combined with, one of 3 cholinesterase inhibitors.

Update (6/04): The combination of a cholinesterase inhibitor with memantine "resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated" JAMA. 2004 Jan 21; 291(3):317-24.

Update (1/04): Forest Laboratories started selling memantine here in January, 2004 under the brand name Namenda, for patients with moderate to severe Alzheimer's symptoms.

Update (9/03): The FDA advisory committee has recommended approval of memantine (which is sold under the name "Namenda") for moderate to severe AD. The positive results described below have were confirmed in a major US study (New England Journal of Medicine). Forest Laboratories in the US will distribute memantine. They have results on the combination use of memantine combined with donepezil (Aricept) that look promising. They say, "Previously patients with moderate disease had only one class of options; now they have an additional therapy available." Since memantine blocks glutamate, unlike the other drugs on the market, it might be used in combination with one of the drugs that stimulate acetylcholine. However, Forest Laboratories Inc. said that memantine "did not significantly improve awareness and reasoning in patients with mild to moderate Alzheimer's disease", and the other drugs may not be of much use with severe AD.

Memantine is a potential neuroprotectant against the chemicals that cells damaged by Alzheimer's release. Memantine for Alzheimer's Diesease is an orally-available compound that acts to modulate the N-methyl-D-aspartate ("NMDA") receptor in the central nervous system. Modulating the NMDA receptor may restore functional neuronal impairment associated with a number of disorders, including chronic conditions of neuropathic pain, dementia, and Alzheimer's disease, as well as acute conditions of traumatic brain injury and stroke. It influences the cell destruction by affecting glutamate activity.

Rive et al* demonstrated improvement in functional independence and reduction in required level of care in advanced Alzheimer's. Merz has marketed Memantine in Germany since 1989 for the treatment of "dementia syndrome", presumably moderate to severe Alzheimer's. Memantine has a mechanism dissimilar for the other available drugs; it counters the "neurotoxic effects of glutamate overload", thereby preventing the elevation of glutamate (which acts destructively upon cholinergic neurons).

*Rive B, Vercelletto M, Damier FD, Cochran J, Francois C. Memantine enhances autonomy in moderate to severe Alzheimer's disease. Int J Geriatr Psychiatry. 2004 May;19(5):458-64.