memantine
Brand: Namenda, Namenda XR, Namzaric (with donepezil)
Prototype Drug
Drug Class: NMDA receptor antagonist
Drug Family: antidementia
Subclass: uncompetitive, low-affinity NMDA receptor antagonist
Organ Systems: cns
Mechanism of Action
Uncompetitive, voltage-dependent NMDA receptor antagonist with moderate affinity; blocks the receptor only when it is chronically activated by excessive glutamate (pathological condition in AD), but allows normal physiological activation. Excessive glutamate activity (excitotoxicity) contributes to neuronal death in Alzheimer's disease; memantine reduces this neurotoxic signal while preserving normal glutamatergic neurotransmission.
NMDA (N-methyl-D-aspartate) glutamate receptor
Indications
- moderate to severe Alzheimer's disease (monotherapy or combination with cholinesterase inhibitor)
Contraindications
- severe renal impairment (use with caution; dose adjustment required)
Adverse Effects
Common
- dizziness
- headache
- constipation
- confusion
- agitation
Serious
- hallucinations
- seizures (rare)
- cardiac effects (AV block rarely reported)
Pharmacokinetics (ADME)
| Absorption | well absorbed orally; bioavailability ~100%; food has no effect |
| Distribution | protein binding ~45%; Vd ~9-11 L/kg |
| Metabolism | minimal hepatic metabolism (~57% excreted unchanged) |
| Excretion | primarily renal; alkaline urine decreases excretion; dose adjustment required for severe renal impairment |
| Half-life | 60-80 hours |
| Onset | weeks for clinically meaningful cognitive effect |
| Peak | 3-7 hours |
| Duration | 24 hours |
| Protein Binding | 45% |
| Vd | 9-11 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| urinary alkalinizers (sodium bicarbonate, carbonic anhydrase inhibitors) | decrease renal clearance of memantine; increase levels | moderate |
| other NMDA antagonists (ketamine, amantadine, dextromethorphan) | additive NMDA blockade; psychosis risk | moderate |
| cholinesterase inhibitors | complementary mechanisms; combination is FDA-approved and synergistic in moderate-severe AD | beneficial |
Nursing Considerations
- Dose adjustment required in severe renal impairment (CrCl 5-29 mL/min: target 5 mg twice daily rather than standard 10 mg twice daily); assess renal function before initiating.
- Combination with donepezil (as Namzaric) targets both cholinergic deficit (donepezil) and glutamate excitotoxicity (memantine) simultaneously; this combination is the most commonly prescribed pharmacotherapy for moderate-severe AD.
- Manage patient and family expectations: memantine slows cognitive decline rather than reversing it; benefits are measured in reduced rate of functional and cognitive deterioration.
- Constipation is common in the elderly; ensure adequate hydration and dietary fiber; document bowel function at each assessment.
Clinical Pearls
- Memantine is the only Alzheimer's drug with a mechanism targeting glutamatergic excitotoxicity rather than cholinergic deficiency, making it complementary (rather than redundant) to cholinesterase inhibitors — the rationale for the approved combination (Namzaric).
- Memantine's low-affinity, voltage-dependent mechanism is crucial to its safety profile: it only blocks the NMDA receptor during pathologically prolonged activation, allowing normal synaptic transmission needed for learning and memory to proceed unimpeded.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.