NAMENDA ® (memantine hydrochloride) is being evaluated as a potential neuroprotectant or neuromodulatory drug to treat progressive neurological impairment due to neuronal injury. Memantine 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.
A major contributing factor to neuronal injury is the over-activation of N-methyl-D-asparate (NMDA) receptors located on cell membranes. Continued over-action leads to neurologic deficits. Thus, drugs that inhibit the over-activity of NMDA receptors have the potential to treat a number of serious conditions, including neuropathy and Alzheimer's disease.
In addition, in response to head injury, brain tumors or stroke, impaired neurons release excessive amounts of glutamate and toxic levels of calcium that enter surrounding cells, facilitating a progressively destructive process. Unlike other NMDA receptor agonists, Memantine acts to modulate the NMDA receptor calcium channel rather than blocking it completely, thus protecting the nervous system from this "exicitoxicity" by reducing the toxic influx of calcium while permitting normal signal transmission between cells.
Alzheimer's Disease
Although the exact sequence of events that lead to Alzheimer's disease and the recognized loss of cognitive function are still being studied, physiologically, this function appears to be destroyed by the pathologic process of the formation and accumulation of toxic amyloid proteins that impair certain neurotransmitter pathways.
Of the two primary neurotransmitter pathways, glutamate, in particular, transmits signals between nerve cells in areas of the brain associated with learning and memory. A growing body of data has established a link between neuronal deficits and increased susceptibility to NMDA receptor-mediated glutamate toxicity.
Diabetic Neuropathy
Diabetic neuropathy is a chronic unrelenting pain that arises when a diabetic patient's nerves are damaged. These damaged nerves send abnormal signals that the brain interprets as pain. Modulating the pain signals, which induce chronic abnormal pain, could result in pain relief for the one million diabetic patients who experience these chronic pain symptoms every year and currently have no adequately effective drug options. While no product is currently approved for this indication, memantine has been shown in clinical studies to effectively reduce nocturnal pain intensity compared to placebo.
A Growing Neuroprotection Market
- Alzheimer's disease and dementia are among the fastest-growing disease states world-wide
- As many as 10% of people over 65 years of age have Alzheimer's
- 800,000 diabetic patients are treated for symptoms of neuropathy in the U.S. annually
- Overall, current drug therapies for diabetic neuropathic pain are sub-optimal