Pharmacology · NMDA receptor antagonists (anti-dementia)
Memantine !
An NMDA receptor blocker for moderate to severe Alzheimer disease. It eases symptoms modestly and is cleared by the kidney.
Updated 2026-11-01
The figure shows memantine in the channel pore of the rat GluN1-GluN2B NMDA receptor, which is very similar to the human receptor.
Mechanism of action
Memantine is a low-to-moderate affinity, uncompetitive (open-channel) NMDA receptor antagonist. It enters the pore only when the channel opens and leaves quickly, damping the constant excess activation thought to come from too much glutamate in Alzheimer disease. There is no evidence that it slows neurodegeneration.
- Excess glutamate keeps NMDA channels open
- Memantine enters and plugs the open pore
- It leaves quickly, sparing normal signals
- Cognition and daily function improve modestly
Pharmacokinetics
- Absorption
- Well absorbed by mouth
- Elimination
- Mostly by the kidney, about half unchanged; partly by tubular secretion
- Half-life
- Long: about 60 to 80 hours; longer in kidney failure
Indications
- Moderate to severe dementia of the Alzheimer type, alone or with a cholinesterase inhibitor Alzheimer disease →
Adverse effects
Common
- Dizziness
- Headache
- Confusion
- Constipation
Contraindications
- Hypersensitivity to memantine or excipients
Key interactions
- Drugs or states that make urine alkaline (sodium bicarbonate, carbonic anhydrase inhibitors, renal tubular acidosis, severe urinary infection)
- Less urinary excretion and higher memantine levels
- Other NMDA antagonists: amantadine, ketamine, dextromethorphan
- Not systematically studied; used with caution
- Drugs using the renal cation transporter (hydrochlorothiazide, triamterene, metformin, cimetidine)
- Possible changes in levels of both drugs
What is monitored
- Cognition, behaviour and daily function
- Kidney function (creatinine clearance)
- Dizziness and fall risk
Administration and safety
- Oral tablets, extended-release capsules and oral solution exist; they are not interchangeable one for one
- The dose is increased in steps
- Caregivers often give the medicine: clear written instructions help
Nursing care
- Assess baseline cognition and behaviour and report changes
- Check kidney function before and during treatment
- Teach caregivers about dizziness and fall prevention
- Ask about diet changes or antacids that alkalinize urine
Pregnancy and breastfeeding
There are no adequate human data; in rats, high doses affected fetal growth.
Test yourself
Think of the answer, then tap the question to see it.
What is the mechanism of memantine?
Uncompetitive, open-channel blockade of NMDA glutamate receptors, with low to moderate affinity.
Can memantine be combined with donepezil?
Yes. They act on different systems (glutamate and acetylcholine) and are often combined in moderate to severe Alzheimer disease.
Why does kidney function matter with memantine?
It is cleared mainly by the kidney, so levels and half-life rise in kidney failure and the dose is adjusted.
Related drugs
Related conditions
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - MEMANTINE HYDROCHLORIDE tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); Memantine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.