Memantine

Mechanism of Action

Neurodegenerative dementia may involve malfunctioning glutamatergic neurotransmission at N-methyl-D-aspartate (NMDA) receptors. Memantine is a voltage dependent, moderate affinity uncompetitive antagonist at NMDA receptors.

It blocks NMDA receptor channels when they are excessively activated by glutamate, helping to reduce pathological calcium influx into neurons.

Importantly, memantine does not completely inhibit NMDA receptor activity. It allows physiological glutamatergic neurotransmission to continue, helping to preserve normal neuronal function.

By TeachMeSeries Ltd (2026)

Fig 1
Mechanism of Action for Memantine

Pharmacokinetics

Absorption

Administered orally, with a bioavailability of ~ 100%. Peak plasma concentrations occur between 3 and 8 hours. 

Distribution

45% plasma protein binding, volume of distribution 10L/kg

Metabolism

Some metabolism, to inactive metabolites. Memantine is not significantly metabolised by cytochrome P450 enzymes.

Excretion

Primarily excreted renally, with more than 99% of the recovered dose eliminated through the kidneys. The elimination half-life is approximately 60–100 hours. A dose adjustment is required in renal impairment. 

Contraindications

Hypersensitivity to active substance or any of its excipients

Adverse Effects and Cautions

Commonly reported adverse effects include headache, dizziness, drowsiness, constipation, shortness of breath and hypertension. 

Caution should be applied in patients with risk of convulsions such as in epilepsy., as memantine increases the risk of convulsions.

A raised urinary pH, such as due to changes in diet or ingestion of alkalising gastric buffers, renal tubular acidosis or severe urinary tract infections with proteus bacteria may reduce the excretion of memantine (by a factor of 7-9) and therefore increase the exposure. 

Interactions

Dopaminergic medicines and anticholinergics

The effects of levodopa, dopaminergic agonists and anticholinergics may be increased when administered alongside memantine

Barbiturates and antipsychotics

The effects of barbiturates and antipsychotics may be reduced by concomitant administration of memantine.

Other NMDA receptor antagonists

Concomitant use of memantine with other NMDA receptor antagonists, particularly amantadine, ketamine and dextromethorphan, should be avoided due to the potential for increased central nervous system adverse effects, including pharmacotoxic psychosis. A possible interaction with phenytoin has also been reported.

Medicines using the renal cationic transport system

Cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine use the same renal cationic transport system as amantadine, therefore may also pose a risk of increased memantine plasma levels.

Hydrochlorothiazide

Reduced exposure of hydrochlorothiazide may occur when administered alongside memantine.

Warfarin

Isolated increases in international normalised ratio (INR) have been reported in warfarinised patients, therefore INR monitoring is recommended.

References

1. Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan DJ. Rang & Dale’s Pharmacology. 9th ed. London: Elsevier; 2019.
2. Alzheimer’s disease – Treatment – NHS Accessed 21/10/26
3. Memantine hydrochloride 10 mg film-coated tablets – Summary of Product Characteristics (SmPC) – (emc) | 716  Accessed 26/10/26