Memantine | NMDA Antagonist | CAS 19982-08-2 | Alzheimer's

Product Name: Memantine
CAS No.: 19982-08-2 (base)
Chemical Name: 1-amino-3,5-dimethyladamantane
Molecular Formula: C₁₂H₂₁N
Appearance: White or almost white crystalline powder
Solubility: Memantine hydrochloride is freely soluble in water and ethanol
Stability: Relatively stable when stored
Common salt: Hydrochloride

1. Introduction

Memantine is a non-competitive NMDA (N-methyl-D-aspartate) receptor antagonist. It modulates the effects of pathologically elevated glutamate levels, preventing neuronal dysfunction. It is used for the treatment of moderate to severe Alzheimer's disease.

Alzheimer's disease is the most common cause of dementia in the elderly, characterized by progressive cognitive decline. One mechanism involved in the pathogenesis of this disease is glutamate excitotoxicity, caused by chronic hyperactivation of NMDA receptors. Memantine, acting as a non-competitive antagonist of these receptors with moderate affinity, helps normalize their function and protect neurons from damage.

2. Chemical Structure & Synthesis

Memantine is an adamantane derivative with an amino group.

Synthesis: Memantine is synthesized from 1-bromo-3,5-dimethyladamantane. The key step is the introduction of the amino group, which can be achieved by reaction with sodium amide in liquid ammonia (Ritter reaction followed by hydrolysis) or through other intermediates. It is typically used as the hydrochloride salt.

3. Mechanism of Action

Memantine is a non-competitive (open-channel) antagonist of NMDA receptors with moderate affinity and fast binding/dissociation kinetics.

• At pathologically elevated glutamate concentrations observed in neurodegenerative diseases, prolonged activation of NMDA receptors occurs, leading to excessive calcium ion influx into neurons and triggering a cascade of reactions resulting in neuronal dysfunction and death (excitotoxicity)

• Memantine blocks NMDA receptor ion channels, preventing excessive calcium influx, but does not disrupt normal physiological activation of receptors by transient glutamate peaks, which are important for learning and memory processes

This "use-dependency" property distinguishes memantine from other NMDA receptor antagonists.

4. Pharmacokinetics

Well absorbed after oral administration; bioavailability approaches 100%. Food intake does not affect absorption. Low plasma protein binding (approximately 45%). Minimally metabolized in the liver. Excreted primarily unchanged by the kidneys via tubular secretion. Half-life is 60–80 hours.

5. Applications

• Treatment of moderate to severe Alzheimer's type dementia – memantine may improve cognitive function, daily living activities, and reduce the severity of behavioral disturbances in patients with Alzheimer's disease

• Other conditions – being investigated for use in other conditions associated with glutamatergic dysfunction (e.g., vascular dementia, Parkinson's disease, neuropathic pain), but official indications are limited to Alzheimer's disease

6. Conclusion

Memantine is an important drug for the symptomatic treatment of Alzheimer's disease, acting on the brain's glutamate system. Its unique mechanism of action reduces excitotoxicity without disrupting normal neurotransmission, helping to improve cognitive function and quality of life of patients. Tolerability of memantine is generally good, but like any drug, it may cause side effects and should be prescribed by a physician.