First U.S. Trial of Memantine for Moderate-to-Severe AD

Cholinesterase inhibitors (ChEIs) are the only drug class currently approved in the U.S. for symptomatic treatment of Alzheimer's disease (AD). Recent challenges to the cholinergic . . .

Cholinesterase inhibitors (ChEIs) are the only drug class currently approved in the U.S. for symptomatic treatment of Alzheimer's disease (AD). Recent challenges to the cholinergic hypothesis, at least in mild-to-moderate AD, have led to pharmacologic assessment of other potentially relevant neurotransmitters (JAMA 2000; 281:1401, and Ann Neurol 2002; 51:145). Excitotoxic neuronal damage resulting from chronic glutamatergic overstimulation, via the postsynaptic glutamatergic receptor, N-methyl-D-aspartate (NMDA), has been postulated as an underlying mechanism of AD (N Engl J Med 1994; 330:613, and Progress in Brain Research 1998; 116:421). Memantine, a noncompetitive NMDA-receptor antagonist, has for years been used in Europe for treatment …

Reviewing Authors

John C. Morris, MD

Jeffrey Burns, MD