Memantine

Memantine has been available for over 10 years in Germany and is the most frequently prescribed treatment for dementia.

Research suggests that memantine is clinically safer than many other NMDA antagonists in treating neurodegenerative diseases.  It's believed that memantine's neuroprotective effects are due to blocking the NMDA receptor against excitotoxicity (overstimulation of glutamate) without upsetting the neurotransmitter's normal functioning as some other drugs do.

Clinical data, demonstrating the ability of memantine to preserve cognition and daily functioning and delay the rate of decline in patients with advanced Alzheimer disease, was presented at a major neuropsychopharmacology conference held in Hawaii in December 2001. 

A second study presented at this meeting shows memantine's potential neuroprotective and cognition-enhancing role in beta-amyloid-induced neurotoxicity in the brain.  Plaques containing beta-amyloid are believed to be a key contributing factor in the development of Alzheimer disease. 

Memantine is currently under Phase III development in the United States by Forest Laboratories.  Researchers believe that Memantine's mechanism of action is distinctly different from agents currently available to treat Alzheimer disease.  All of these agents increase the availability of the neurotransmitter acetylcholine for viable neurons, whereas memantine is thought to prolong or preserve neuronal viability. 

Research suggests memantine may exert a neuroprotective effect and improve cognition when beta-amyloid toxicity is present. Previous research suggests that formation of beta-amyloid containing plaques in the brain, and progressive nerve-cell death, are primary causes of the cognitive and functional deteriorations of Alzheimer disease. 
In the study researchers observed the degeneration of neurons in rat brains following injections with beta-amyloid. Animals treated with memantine, however, had significant reductions in the amount of neuronal degeneration and performed better on other key measures of behavioral and functional changes. The researchers concluded that memantine has the potential to protect against neuronal degradation in rats and may slow the learning impairment caused by beta-amyloid. 

The investigational agent memantine is thought to provide a neuroprotective effect in both the central and peripheral nervous systems by blocking the NMDA receptor against the effects of chronic excess amounts of glutamate, but without interfering with the role of glutamate in normal neuronal functioning. The mechanism of action of memantine differs from earlier investigational NMDA antagonists that interfered with normal glutamate functioning due to their high affinity to the receptor. 

Glutamate plays an integral role in neural pathways associated with learning and memory, including the movement of electrical signals across up to 70% of the central nervous system's excitatory synapses. Excessive amounts of glutamate can, however, damage cells by causing overstimulation. The excitotoxicity produced by glutamate is hypothesized to be responsible for the neuronal cell death observed in Alzheimer, and possibly in other diseases that involve neurodegeneration. 

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