Memantine

Primer

Memantine is used to treat moderate to severe Alzheimer's disease. It acts on the glutamatergic system by blocking NMDA receptors.

Indications

Memantine is indicated for the treatment of patients with moderate to severe AD (i.e. - the MMSE score must be < 20).[1]

Mechanism of Action

  • NMDA receptor antagonist that helps prevent excitotoxicity (mediated by Ca2+)
  • Glutamate is the main excitatory neurotransmitter in the brain, and acts at NMDA receptors. Memantine blocks NMDA receptors and so may reduce the negative effects of glutamate, namely the excitotoxicity pathway via NMDA receptor over-activation, which is thought to prevent cell death.
  • Memantine may also be neuroprotective.

Dosing

  • Week 1: 5 mg PO qAM as the starting dose
  • Week 2: 5 mg PO BID
  • Week 3: 10mg PO qAM, 5mg PO qHS
  • Week 4: 10 mg PO BID

Renal

  • Dose should be halved in patients with renal impairment.[2]

Contraindications

Contraindications use with caution in patients with severe hepatic or renal impairment

Side Effects

Memantine is generally well tolerated. Most common side effects may include insomnia, diarrhea, urinary incontinence, confusion, dizziness, or agitation.

Drug-Drug Interactions

No major drug interactions.

References

1) Atri, A., Molinuevo, J. L., Lemming, O., Wirth, Y., Pulte, I., & Wilkinson, D. (2013). Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapy. Alzheimer's research & therapy, 5(1), 6.
2) Moritoyo, T., Hasunuma, T., Harada, K., Tateishi, T., Watanabe, M., Kotegawa, T., ... & Fukuoka, T. (2012). Effect of renal impairment on the pharmacokinetics of memantine. Journal of pharmacological sciences, 119(4), 324-329.