Drug/Small Molecule:
memantine

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PharmGKB contains no drug labels with pharmacogenomic information for this drug/small molecule. To report a drug label with PGx, click here.

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs1523130 -1663T>C, 119499507T>C, 25994653T>C, 5177T>C
T > C
5' UTR
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • DMAA
  • Memantina [INN-Spanish]
  • Memantine HCL
  • Memantine Hydrochloride
  • Memantine [INN]
  • Memantinum [INN-Latin]
  • memantine
Trade Names
  • Ebixa
  • Namenda
Brand Mixture Names

PharmGKB Accession Id:
PA10364

Description

Memantine is an amantadine derivative with low to moderate-affinity for NMDA receptors. It is a noncompetitive NMDA receptor antagonist that binds preferentially to NMDA receptor-operated cation channels. It blocks the effects of excessive levels of glutamate that may lead to neuronal dysfunction. It is under investigation for the treatment of Alzheimer's disease, but there has been no clinical support for the prevention or slowing of disease progression.

Source: Drug Bank

Indication

For the treatment of moderate to severe dementia of the Alzheimer's type.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Memantine exerts its action through uncompetitive NMDA receptor antagonism, binding preferentially to the NMDA receptor-operated cation channels. Prolonged increased levels of glutamate in the brain of demented patients are sufficient to counter the voltage-dependent block of NMDA receptors by Mg 2+ ions and allow continuous influx of Ca 2+ ions into cells, ultimately resulting in neuronal degeneration. Studies suggest that memantine binds more effectively than Mg 2+ ions at the NMDA receptor, and thereby effectively blocks this prolonged influx of Ca 2+ ions through the NMDA channel whilst preserving the transient physiological activation of the channels by higher concentrations of synaptically released glutamate. Thus memantine protects against chronically elevated concentrations of glutamate. Memantine also has antagonistic activity at the type 3 serotonergic (5-HT 3) receptor with a potency that is similar to that at the NMDA receptor, and lower antagonistic activity at the nicotinic acetylcholine receptor. This drug has no affinity for gamma-aminobutyric acid (GABA), benzodiazepine, dopamine, adrenergic, histamine, or glycine receptors or for voltage-dependent calcium, sodium, or potassium channels.

Source: Drug Bank

Pharmacology

Memantine, an amantadine derivative, is an NMDA receptor antagonist used in the treatment of Alzheimer's disease. It differs from traditional agents used in Alzheimer's disease by acting on glutamatergic neurotransmission, rather than cholinergic. There is some evidence that dysfunction of glutamatergic neurotransmission, manifested as neuronal excitotoxicity, is involved in the aetiology of Alzheimer's disease (Cacabelos et al., 1999). As such, targeting the glutamatergic system, specifically NMDA receptors, was a novel approach to treatment in view of the limited efficacy of existing drugs targeting the cholinergic system. A systematic review of randomised controlled trials found that memantine has a positive effect on cognition, mood, behaviour, and the ability to perform daily activities. There is no evidence that memantine prevents or slows neurodegeneration in patients with Alzheimer's disease.

Source: Drug Bank

Food Interaction

Take without regard to meals.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Excreted largely unchanged. About 20% is metabolized to 1-amino-3-hydroxymethyl-5-methyl-adamantane and 3-amino-1-hydroxy-5,7-dimethyl-adamantane.

Source: Drug Bank

Protein Binding

45%

Source: Drug Bank

Absorption

Well absorbed orally with a bioavailability of approximately 100%. Peak plasma concentrations are reached in 3-7 hours. Food has no effect on absorption.

Source: Drug Bank

Half-Life

60-100 hours

Source: Drug Bank

Toxicity

Side effects include pain, abnormal crying, leg pain, fever, increased apetite. Adverse drug reactions include: dizziness, confusion, headache, hallucinations, tiredness. Less common side effects include: vomiting, anxiety, hypertonia, cystitis, and increased libido. Doses of up to 400 mg have been tolerated.

Source: Drug Bank

Route of Elimination

Memantine undergoes partial hepatic metabolism. About 48% of administered drug is excreted unchanged in urine; the remainder is converted primarily to three polar metabolites which possess minimal NMDA receptor antagonistic activity: the N-glucuronide conjugate, 6-hydroxy memantine, and 1-nitroso-deaminated memantine. It is excreted predominantly in the urine, unchanged.

Source: Drug Bank

Volume of Distribution

  • 9 to 11 L/kg

Source: Drug Bank

Chemical Properties

Chemical Formula

C12H21N

Source: Drug Bank

Isomeric SMILES

CC12CC3CC(C1)(CC(C3)(C2)N)C

Source: OpenEye

Canonical SMILES

CC12CC3CC(C)(C1)CC(N)(C3)C2

Source: Drug Bank

Average Molecular Weight

179.3018

Source: Drug Bank

Monoisotopic Molecular Weight

179.167399677

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
NR1I2

Drug Targets

Gene Description
GRIN2A (source: Drug Bank)
GRIN2B (source: Drug Bank)
GRIN3A (source: Drug Bank)
HTR3A (source: Drug Bank)

Drug Interactions

Drug Description
memantine Possible increased levels of memantine (source: Drug Bank)
memantine Possible increased levels of memantine (source: Drug Bank)
memantine Increased risk of CNS adverse effects with this association (source: Drug Bank)
memantine Increased risk of CNS adverse effects with this association (source: Drug Bank)
memantine Increased risk of CNS adverse effects (source: Drug Bank)
memantine Increased risk of CNS adverse effects (source: Drug Bank)
acetazolamide Possible increased levels of memantine (source: Drug Bank)
acetazolamide Possible increased levels of memantine (source: Drug Bank)
amantadine Increased risk of CNS adverse effects with this association (source: Drug Bank)
amantadine Increased risk of CNS adverse effects with this association (source: Drug Bank)
dextromethorphan Increased risk of CNS adverse effects with this association (source: Drug Bank)
dextromethorphan Increased risk of CNS adverse effects with this association (source: Drug Bank)
dichlorphenamide Possible increased levels of memantine (source: Drug Bank)
ketamine Increased risk of CNS adverse effects with this association (source: Drug Bank)
ketamine Increased risk of CNS adverse effects with this association (source: Drug Bank)
methazolamide Possible increased levels of memantine (source: Drug Bank)
methazolamide Possible increased levels of memantine (source: Drug Bank)
sodium Possible increased levels of memantine (source: Drug Bank)
sodium bicarbonate Possible increased levels of memantine (source: Drug Bank)
memantine Possible increased levels of memantine (source: Drug Bank)
memantine Possible increased levels of memantine (source: Drug Bank)

Curated Information ?

EvidenceDisease
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Dementia

Publications related to memantine: 3

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Population pharmacokinetic study of memantine: effects of clinical and genetic factors. Clinical pharmacokinetics. 2013. Noetzli Muriel, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Assessment of the impact of renal impairment on systemic exposure of new molecular entities: evaluation of recent new drug applications. Clinical pharmacology and therapeutics. 2009. Zhang Y, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
100 years and counting: prospects for defeating Alzheimer's disease. Science (New York, N.Y.). 2006. Roberson Erik D, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0456-3205-60
DrugBank:
DB01043
KEGG Compound:
C13736
PubChem Compound:
4054
PubChem Substance:
46506702
586325
Drugs Product Database (DPD):
2260638
BindingDB:
50062599
ChemSpider:
3914
Therapeutic Targets Database:
DAP000493
FDA Drug Label at DailyMed:
b9f27baf-aa2a-443a-9ef5-e002d23407ba

Clinical Trials

These are trials that mention memantine and are related to either pharmacogenetics or pharmacogenomics.

Common Searches

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.