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.
Food and Drug Administration (FDA) Indication
Other Uses (non-FDA approved)
Diagnosis of Alzheimer 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.
Memantine is an uncompetitive antagonist of the NMDA subtype of glutamate receptors in the CNS. Alzheimer disease is believed to be caused by overstimulation of glutamate, the primary excitatory amino acid in the CNS, resulting in excitotoxicity and neuronal degeneration. The NMDA receptor is a voltage-gated cation channel that in the physiologic unstimulated state is blocked by magnesium ions. Stimulated magnesium is displaced allowing calcium influx and activation. In Alzheimer disease, there is pathologic overstimulation of the receptor causing it to be in a chronically active state. Memantine helps to counteract the excessive stimulation.
Memantine also exhibits antagonist activity at the serotonergic type 3 (5-HT3) and nicotinic acetylcholine receptors. It has no activity at the gamma-aminobutyric acid (GABA), benzodiazepine, dopamine, adrenergic, histamine, or glycine receptors or for voltage-dependent calcium, sodium, or potassium channels.
Switching from Immediate-Release (IR) to Extended-Release (ER)
Most common in clinical trials: Dizziness, headache, confusion, diarrhea, and constipation
Others: Fatigue, pain, hypertension, weight gain, hallucination, confusion, aggressive behavior, vomiting, abdominal pain, urinary incontinence
Uncommon (Post-marketing surveillance, clinical trials, or case reports):
Patients with hypersensitivity to memantine hydrochloride or any agents used in the formulation.
No routine monitoring required for toxicity.
Time to peak concentrations
Time to Peak Concentrations
Terminal Elimination Half-Life