Memantine has been used for more than a decade to treat dementia in Germany. Last year, it was approved for treatment of moderate to severe Alzheimer's in other European countries (see ARF related news story), and the manufacturers sought approval for its use in the U.S. (see ARF related news story) and other ARF news story).

The use of memantine for Alzheimer's is based on the theory that excessive activation of N-methyl-D-aspartate (NMDA) receptors may underlie the degeneration of cholinergic cells, leading to cognitive, social, and motor deficits. Memantine, a fast, voltage-dependent NMDA receptor antagonist, blocks the NMDA receptor in the presence of sustained release of low glutamate concentrations, and thus attenuates NMDA receptor function. Theoretically, memantine might protect vulnerable neurons, thus slowing the progression of the disease rather than just providing temporary symptomatic relief, as is thought to be the case with cholinesterase inhibitors.

In the present study, funded by Merz Pharmaceuticals, researchers found benefits after 28 weeks of the double-blind, parallel-group, placebo-controlled study. Relative to the placebo group, patients on memantine had significantly higher scores on a primary test of daily living ability (ADCS-ADLsev) and several secondary tests of function and cognitive performance (FAST and SIB). The authors noted the lack of gastrointestinal side effects seen with cholinesterase inhibitors as another advantage of memantine.

The study design did not provide evidence on whether the symptomatic improvement reflected a slowing of the underlying neurodegeneration. Also, it is impossible to reliably compare the efficacy of memantine directly to that of cholinesterase inhibitors, as studies of the latter drugs have primarily been done in patients with milder disease.-Hakon Heimer.

Reference:
Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ. Memantine in moderate to severe Alzheimer's disease. N Engl J Med. 2003 Apr 3;348(14):1333-41. Abstract