Memantine is a non-competitive, moderate-affinity N-methyl-D-aspartate (NMDA) receptor antagonist. It is a disease-modifying agent used primarily for the treatment of moderate to severe Alzheimer's disease (AD). It works by regulating glutamate activity, preventing excitotoxicity and neuronal damage, thereby slowing cognitive decline and improving daily functioning in patients. In the Indian context, it is a first-line pharmacological agent for advanced dementia.
Adult: For Alzheimer's Disease: Start at 5 mg once daily. Increase in increments of 5 mg per week to the target maintenance dose of 10 mg twice daily (20 mg/day). The recommended titration schedule is: Week 1: 5 mg once daily; Week 2: 5 mg twice daily; Week 3: 10 mg (morning) and 5 mg (evening); Week 4 and maintenance: 10 mg twice daily.
Note: Can be taken with or without food. Tablet should be swallowed whole with water. Do not crush or chew. For patients on 10 mg/day, a single daily dose is acceptable. Twice-daily dosing may improve tolerability. If a dose is missed, do not double the next dose. Resume the regular schedule.
Memantine acts as a low-to-moderate affinity, non-competitive (open-channel) antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. In Alzheimer's disease, chronic neurodegeneration is associated with glutamatergic excitotoxicity. Pathological, sustained elevation of glutamate over-activates NMDA receptors, leading to excessive calcium influx, mitochondrial dysfunction, and neuronal apoptosis. Memantine preferentially blocks the NMDA receptor-associated ion channel when it is pathologically activated by prolonged, low-level glutamate exposure (as in AD), but allows for normal physiological transient activation required for synaptic plasticity and learning. This voltage-dependent, fast off-rate kinetics are key to its therapeutic window.
Pregnancy: Pregnancy Category B (Animal studies show no risk, but no adequate human studies). Use only if potential benefit justifies potential risk to the fetus. Not indicated in women of childbearing potential.
Driving: Memantine may cause dizziness, somnolence, and confusion, especially during titration. Patients should be cautioned about operating machinery or driving until they are certain the medication does not affect them adversely.
| Other NMDA Antagonists (Amantadine, Ketamine, Dextromethorphan) | Increased risk of CNS toxicity (dizziness, confusion, psychosis). Additive pharmacodynamic effects. | Major |
| Drugs that alkalinize urine (Carbonic Anhydrase Inhibitors: Acetazolamide; Sodium Bicarbonate) | Markedly decreases renal excretion of memantine, leading to increased plasma levels and risk of toxicity. | Major |
| Cimetidine, Ranitidine, Hydrochlorothiazide, Quinidine | Competes for renal tubular cationic secretion, potentially increasing memantine plasma levels. Monitor for adverse effects. | Moderate |
| Cholinesterase Inhibitors (Donepezil, Rivastigmine, Galantamine) | Pharmacologically complementary. Used together safely. No significant PK interaction. May have additive therapeutic benefit. | Minor (Therapeutic combination) |
| Anticholinergic drugs (e.g., Trihexyphenidyl, Oxybutynin) | May theoretically worsen cognitive function or counteract cholinergic effects of co-administered cholinesterase inhibitors. | Moderate |
| Levodopa, Dopamine Agonists | Memantine has weak D2 agonism; may have additive effects or side effects. | Moderate |
| Alcohol | May enhance CNS depressant effects (dizziness, confusion). | Moderate |