Memantine is an antagonist of the NMDA (N-Methyl-D-Aspartate)-receptor subtype of glutamate receptor. It is used to slow the neurotoxicity thought to be involved in Alzheimer disease and other neurodegenerative diseases. Memantine blocks the NMDA-receptor subtype of glutamate receptors preventing over-activation of glutamine receptors while allowing the normal activity. Its blocking effects antagonize an overactive glutaminergic system in the central nervous system (CNS) which is thought to be involved in the neurotoxicity seen in Alzheimer disease.
- NMDA-receptor antagonist
- Chemical name: 1-amino-3,5-dimethyladamantane hydrochloride
- Molecular formula: C12H21N•HCl
- Molecular weight: 215.76
Food and Drug Administration (FDA) Indication
- Treatment of moderate to severe Alzheimer dementia
Other Uses (non-FDA approved)
- Mild to moderate Alzheimer dementia
- Mild to moderate vascular dementia
- Chronic pain
- Psychiatric disorders
- Mild cognitive impairment
Diagnosis of Alzheimer Disease
- The DSM-5 criteria for diagnosis include the following characteristics:
- Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains: complex attention, executive function, learning, and memory, language, perceptual-motor or social cognition
- The cognitive deficits interfere with independence in everyday activities
- The cognitive deficits do not occur only in the context of delirium
- Another mental disorder does not better explain the cognitive deficits
- The onset is an insidious and gradual progression of impairment in at least 2 cognitive domains:
- Evidence of a causative Alzheimer disease genetic mutation from family history or genetic testing
- All 3 of the following: Clear evidence of a decline in memory and learning and one or more other domains; steadily progressive, gradual decline in cognition, without extended plateaus; and no evidence of mixed etiology due to other neurodegenerative disorders or cerebrovascular disease.
Role of Memantine in Alzheimer Dementia
Alzheimer disease is a neurodegenerative disorder characterized by the presence of extracellular amyloid-beta protein an intracellular neurofibrillary tangle composed of hyperphosphorylated protein in the brain. There is a decrease in acetylcholine synthesis and impaired cortical cholinergic function in patients with Alzheimer dementia. So cholinesterase inhibitors (like donepezil, rivastigmine, galantamine) in dementia provide symptomatic relief by inhibiting cholinesterase at synaptic cleft and increasing cholinergic transmission. However, the mechanism of action of memantine is distinct from those of cholinergic agents and is proposed to be neuroprotective. Glutamate is a major excitatory neurotransmitter in the brain. One of the receptors activated by glutamate is the NMDA receptor which is essential for processes like learning and memory. Excessive activation of NMDARs been shown to be associated with neuronal loss/damage contributing to various acute and chronic neurological disorders including dementia. However physiological NMDA-receptor activity is also needed for normal neuronal function. Any agents that block all NMDA-receptor activity will have unacceptable clinical side effects. Memantine, through its action as an uncompetitive, low-affinity, open-channel blocker (uncompetitive antagonist of extrasynaptic NMDAR), preferentially enters the receptor-associated ion channel when it is excessively open, and hence, does not interfere with normal synaptic transmission. By doing so, it prevents or protects against further damage from neuronal cell death induced by excitotoxicity. Therefore, memantine is used for the treatment of Alzheimer dementia in combination with acetylcholinesterase inhibitors.