U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C12H21N
Molecular Weight 179.3018
Optical Activity NONE
Defined Stereocenters 0 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MEMANTINE

SMILES

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

InChI

InChIKey=BUGYDGFZZOZRHP-UHFFFAOYSA-N
InChI=1S/C12H21N/c1-10-3-9-4-11(2,6-10)8-12(13,5-9)7-10/h9H,3-8,13H2,1-2H3

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/9120573

NAMENDA (marketed under the brands Namenda among others) is an N-methyl-D-aspartate (NMDA) receptor antagonist indicated for the treatment of moderate to severe dementia of the Alzheimer’s type. Persistent activation of central nervous system N-methyl-D-aspartate (NMDA) receptors by the excitatory amino acid glutamate has been hypothesized to contribute to the symptomatology of Alzheimer’s disease. Memantine is postulated to exert its therapeutic effect through its action as a low to moderate affinity uncompetitive (open-channel) NMDA receptor antagonist which binds preferentially to the NMDA receptor-operated cation channels. There is no evidence that memantine prevents or slows neurodegeneration in patients with Alzheimer’s disease. Memantine showed low to negligible affinity for GABA, benzodiazepine, dopamine, adrenergic, histamine and glycine receptors and for voltage-dependent Ca2+, Na+ or K+ channels. Memantine also showed antagonistic effects at the 5HT3 receptor with a potency similar to that for the NMDA receptor and blocked nicotinic acetylcholine receptors with one-sixth to one-tenth the potency. In vitro studies have shown that memantine does not affect the reversible inhibition of acetylcholinesterase by donepezil, galantamine, or tacrine.

Originator

Curator's Comment: Memantine was first synthesized by Eli Lilly and Company and patented in 1968, as documented in the Merck Index, as a derivative of amantadine, an anti-influenza agent.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NAMENDA

Approved Use

Namenda (memantine hydrochloride) is indicated for the treatment of moderate to severe dementia of the Alzheimer's type.

Launch Date

2003
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
25.34 ng/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEMANTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
19.69 ng/mL
5 mg 14 times / 2 weeks multiple, oral
dose: 5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MEMANTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
6.2 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEMANTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1853 ng × h/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEMANTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
386.37 ng × h/mL
5 mg 14 times / 2 weeks multiple, oral
dose: 5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MEMANTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
540 ng × h/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEMANTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
62 h
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEMANTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
64.57 h
5 mg 14 times / 2 weeks multiple, oral
dose: 5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MEMANTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
66.86 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MEMANTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
400 mg single, oral
Highest studied dose
Dose: 400 mg
Route: oral
Route: single
Dose: 400 mg
Sources:
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources:
Other AEs: Restlessness, Psychosis...
Other AEs:
Restlessness (1 patient)
Psychosis (1 patient)
Visual hallucinations (1 patient)
Somnolence (1 patient)
Stupor (1 patient)
Loss of consciousness (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Loss of consciousness 1 patient
400 mg single, oral
Highest studied dose
Dose: 400 mg
Route: oral
Route: single
Dose: 400 mg
Sources:
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources:
Psychosis 1 patient
400 mg single, oral
Highest studied dose
Dose: 400 mg
Route: oral
Route: single
Dose: 400 mg
Sources:
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources:
Restlessness 1 patient
400 mg single, oral
Highest studied dose
Dose: 400 mg
Route: oral
Route: single
Dose: 400 mg
Sources:
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources:
Somnolence 1 patient
400 mg single, oral
Highest studied dose
Dose: 400 mg
Route: oral
Route: single
Dose: 400 mg
Sources:
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources:
Stupor 1 patient
400 mg single, oral
Highest studied dose
Dose: 400 mg
Route: oral
Route: single
Dose: 400 mg
Sources:
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources:
Visual hallucinations 1 patient
400 mg single, oral
Highest studied dose
Dose: 400 mg
Route: oral
Route: single
Dose: 400 mg
Sources:
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources:
Overview

Overview

OverviewOther

Drug as perpetrator​Drug as victimTox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
[Memantine and neurogenic bladder disorders within the bounds of spastic conditions].
1982
Methyl parathion acute toxicity: prophylaxis and therapy with memantine and atropine.
1990 May-Jun
Inhibition by memantine of the development of persistent oral dyskinesias induced by long-term haloperidol treatment of rats.
1996 Oct
How to overcome resistance of influenza A viruses against adamantane derivatives.
1998 Feb
Anticonvulsants for soman-induced seizure activity.
1999 Mar-Apr
Anticonvulsant efficacy of N-methyl-D-aspartate antagonists against convulsions induced by cocaine.
1999 May
[A comparative study of the central H-cholinergic-blocking and NMDA-blocking actions of MK-801, memantin, amantadine, pyrilen and IEM-1754 in experiments on intact rats].
2000 Mar-Apr
Effects of the NMDA receptor channel blockers memantine and MRZ 2/579 on morphine withdrawal-facilitated aggression in mice.
2000 May
Uncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptors alter the mRNA expression of proteins associated with the NMDA receptor complex.
2001 Feb
The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner.
2001 Jun 22
Involvement of nitric oxide in myotoxicity produced by diisopropylphosphorofluoridate (DFP)-induced muscle hyperactivity.
2002 Dec
A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500).
2002 Nov
The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease.
2003 Fall
Delusions and hallucinations in dementia with Lewy bodies: worsening with memantine.
2005 Aug 9
Development of subtle psychotic symptoms with memantine: a case report.
2005 May
A comparison of the predictive therapeutic and undesired side-effects of the NMDA receptor antagonist, memantine, in mice.
2005 May
Simultaneous liquid chromatographic assay of amantadine and its four related compounds in phosphate-buffered saline using 4-fluoro-7-nitro-2,1,3-benzoxadiazole as a fluorescent derivatization reagent.
2006 May
Effect of BD 1047, a sigma1 receptor antagonist, in the animal models predictive of antipsychotic activity.
2006 Sep-Oct
Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability.
2007 May
Memantine-induced hepatitis with cholestasis in a very elderly patient.
2008 Apr 15
Memantine prevents the cognitive impairment induced by 3,4-methylenedioxymethamphetamine in rats.
2008 Jul 28
Methylmercury increases N-methyl-D-aspartate receptors on human SH-SY 5Y neuroblastoma cells leading to neurotoxicity.
2008 Jul 30
Galantamine-induced pisa syndrome: memantine as an alternative.
2008 Jun
Memantine-induced myoclonus and delirium exacerbated by trimethoprim.
2008 Mar
The attenuating effect of memantine on staurosporine-, salsolinol- and doxorubicin-induced apoptosis in human neuroblastoma SH-SY5Y cells.
2008 Mar-Apr
Ca2+ inhibits the association of memantine with N-methyl-D-aspartate (NMDA) receptor-gated ion channels.
2008 Sep
Does memantine induce bradycardia? A study in the French PharmacoVigilance Database.
2008 Sep
Memanti-nium chloride 0.1-hydrate.
2009 Aug 19
Memantine dosing in patients with dementia.
2009 Feb
Characteristic effects of anti-dementia drugs on rat sleep patterns.
2009 Mar
Treatment of acquired periodic alternating nystagmus with memantine: a case report.
2009 Mar-Apr
Protection of DFP-induced oxidative damage and neurodegeneration by antioxidants and NMDA receptor antagonist.
2009 Oct 15
[Effects of electroacupuncture on expression of Abeta positive cells of the hippocampus and SOD activity in rats with streptozocin-Alzheimer's disease].
2010 Dec
NMDA antagonist memantine improves levodopa-induced dyskinesias and "on-off" phenomena in Parkinson's disease.
2010 Mar 15
Memantine ameliorates scopolamine-induced amnesia in chicks trained on taste-avoidance learning.
2010 May
Inhibition of apoptosis in human retinal pigment epithelial cells treated with benzo(e)pyrene, a toxic component of cigarette smoke.
2010 May
Protective effects of memantine and epicatechin on catechol-induced toxicity on Müller cells in vitro.
2010 May 27
Memantine is a useful drug to prevent the spatial and non-spatial memory deficits induced by methamphetamine in rats.
2010 Nov
Sensitive and rapid HPLC method for determination of memantine in human plasma using OPA derivatization and fluorescence detection: application to pharmacokinetic studies.
2010 Oct-Dec
Antinociceptive Effect of Memantine and Morphine on Vincristine-induced Peripheral Neuropathy in Rats.
2010 Sep
Memantine prevents aluminum-induced cognitive deficit in rats.
2011 Nov 20
The role of memantine in the treatment of psychiatric disorders other than the dementias: a review of current preclinical and clinical evidence.
2012 Aug 1
Memantine in patients with moderate to severe Alzheimer's disease: meta-analyses using realistic definitions of response.
2014
Glial activation and post-synaptic neurotoxicity: the key events in Streptozotocin (ICV) induced memory impairment in rats.
2014 Feb
Patents

Sample Use Guides

Initial dose is 5 mg once daily. Increase dose in 5 mg increments to a maintenance dose of 10 mg twice daily. A minimum of 1 week of treatment with the previous dose should be observed before increasing the dose.
Route of Administration: Oral
Neuronal SK-N-SH cells were treated with 10 uM memantine and was measured levels of secreted total A beta precursor protein APP (sAPP), APP alpha isoform and A beta((1-40)) in a time dependent manner for up to 24h. Memantine significantly decreased the levels of the secreted form of sAPP, sAPP alpha and A beta((1-40)) compared to vehicle treated cells.
Name Type Language
MEMANTINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
3,5-DIMETHYL-1-ADAMANTANAMINE
Systematic Name English
D-145
Code English
MEMANTINE [VANDF]
Common Name English
MEMANTINE [MI]
Common Name English
TRICYCLO(3.3.1.1(SUP 3,7))DECAN-1-AMINE, 3,5-DIMETHYL-
Common Name English
1-AMINO-3,5-DIMETHYLADAMANTANE
Systematic Name English
NEMDATINE
Brand Name English
Memantine [WHO-DD]
Common Name English
NSC-757843
Code English
memantine [INN]
Common Name English
DRG-0267
Code English
3,5-DIMETHYLTRICYCLO(3.3.1.1(SUP 3,7))DECAN-1-AMINE
Systematic Name English
MEMANTINE [HSDB]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1509
Created by admin on Fri Dec 15 15:59:40 GMT 2023 , Edited by admin on Fri Dec 15 15:59:40 GMT 2023
NDF-RT N0000020015
Created by admin on Fri Dec 15 15:59:40 GMT 2023 , Edited by admin on Fri Dec 15 15:59:40 GMT 2023
NCI_THESAURUS C38149
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WHO-ATC N06DX01
Created by admin on Fri Dec 15 15:59:40 GMT 2023 , Edited by admin on Fri Dec 15 15:59:40 GMT 2023
WHO-ATC N06DA52
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WHO-VATC QN06DA52
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NDF-RT N0000175745
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WHO-VATC QN06DX01
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LIVERTOX NBK547981
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WHO-ATC N06DA53
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NDF-RT N0000020015
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EMA ASSESSMENT REPORTS NEMDATINE (AUTHORIZED: ALZHEIMER DISEASE)
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Code System Code Type Description
FDA UNII
W8O17SJF3T
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PRIMARY
SMS_ID
100000085447
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PRIMARY
RXCUI
6719
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PRIMARY RxNorm
INN
3952
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PRIMARY
CAS
19982-08-2
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PRIMARY
EPA CompTox
DTXSID5045174
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PRIMARY
HSDB
7327
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PRIMARY
IUPHAR
4253
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PRIMARY
NCI_THESAURUS
C73269
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PRIMARY
CLINICAL_TRIALS.GOV
NCT03527472
Created by admin on Fri Dec 15 15:59:40 GMT 2023 , Edited by admin on Fri Dec 15 15:59:40 GMT 2023
PRIMARY Memantine for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus (ClearMEMory)
PUBCHEM
4054
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PRIMARY
DRUG CENTRAL
1679
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PRIMARY
NSC
757843
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PRIMARY
EVMPD
SUB08731MIG
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PRIMARY
DAILYMED
W8O17SJF3T
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PRIMARY
DRUG BANK
DB01043
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PRIMARY
WIKIPEDIA
MEMANTINE
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PRIMARY
MERCK INDEX
m7167
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PRIMARY Merck Index
MESH
D008559
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PRIMARY
ChEMBL
CHEMBL807
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PRIMARY
CHEBI
64312
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PRIMARY