Memantine

Class

• NMDA receptor antagonist

Indications

• • Moderate to severe Alzheimer's disease

Administration/Absorption

• • Well absorbed orally with a bioavailability of approximately 100%

  • Peak plasma concentrations are reached in 3-7 hours

Dosage

Distribution

Mechanism

• • Low-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors

  • Binds to the NMDA receptor with a higher affinity than Mg²⁺ ions

    • Therefore able to inhibit the prolonged influx of Ca²⁺ ions, which forms the basis of neuronal excitotoxicity

  • The low affinity and rapid off-rate kinetics of memantine at the level of the NMDA receptor-channel, however, preserves the physiological function of the receptor

    • It can still be activated by the relatively high concentrations of glutamate released following depolarization of the presynaptic neuron

  • Secondary effects of unknown clinical significance:

    • Non-competitive antagonist at the 5HT₃ receptor

    • Non-competitive antagonist at various nicotinic acetylcholine receptors (nAChRs)

Excretion

• • Excreted largely unchanged

    • About 20% is metabolized to 1-amino-3-hydroxymethyl-5-methyl-adamantane and 3-amino-1-hydroxy-5,7-dimethyl-adamantane.

  • Half-life 60-100 hrs

Side effects

• • Confusion, dizziness, drowsiness, headache, insomnia, agitation, and/or hallucinations

Interactions

Contraindications