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

1.0662624E12
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
Methyl parathion acute toxicity: prophylaxis and therapy with memantine and atropine.
1990 May-Jun
How to overcome resistance of influenza A viruses against adamantane derivatives.
1998 Feb
Prevention of cocaine-induced convulsions and lethality in mice: effectiveness of targeting different sites on the NMDA receptor complex.
2000 Jan 28
[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
Uncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptors alter the mRNA expression of proteins associated with the NMDA receptor complex.
2001 Feb
NMDA antagonists inhibit the development of ethanol dependence in rats.
2001 Jan-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
Are neuronal nicotinic receptors a target for antiepileptic drug development? Studies in different seizure models in mice and rats.
2003 Apr 11
The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease.
2003 Fall
Effect of NMDA receptor antagonists on behavioral impairment induced by chronic treatment with dexamethasone.
2005 Jan-Feb
Memantine: a review of its use in Alzheimer's disease.
2006
Visual hallucinations and agitation in Alzheimer's disease due to memantine: report of three cases.
2007 May
[Therapy of Alzheimer's disease: current status and future development].
2008
Effects of memantine on neuronal structure and conditioned fear in the Tg2576 mouse model of Alzheimer's disease.
2008 Dec
Memantine-induced myoclonus and delirium exacerbated by trimethoprim.
2008 Mar
Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer's disease: a pooled analysis of 3 studies.
2008 Mar
Profound pain reduction after induction of memantine treatment in two patients with severe phantom limb pain.
2008 Oct
Does memantine induce bradycardia? A study in the French PharmacoVigilance Database.
2008 Sep
Characteristic effects of anti-dementia drugs on rat sleep patterns.
2009 Mar
Protection of DFP-induced oxidative damage and neurodegeneration by antioxidants and NMDA receptor antagonist.
2009 Oct 15
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
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 Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
NDF-RT N0000020015
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
NCI_THESAURUS C38149
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
WHO-ATC N06DX01
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
WHO-ATC N06DA52
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
WHO-VATC QN06DA52
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
NDF-RT N0000175745
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
WHO-VATC QN06DX01
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
LIVERTOX NBK547981
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
WHO-ATC N06DA53
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
NDF-RT N0000020015
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
EMA ASSESSMENT REPORTS NEMDATINE (AUTHORIZED: ALZHEIMER DISEASE)
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
Code System Code Type Description
FDA UNII
W8O17SJF3T
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
SMS_ID
100000085447
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
RXCUI
6719
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY RxNorm
INN
3952
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
CAS
19982-08-2
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
EPA CompTox
DTXSID5045174
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
HSDB
7327
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
IUPHAR
4253
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
NCI_THESAURUS
C73269
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
CLINICAL_TRIALS.GOV
NCT03527472
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY Memantine for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus (ClearMEMory)
PUBCHEM
4054
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
DRUG CENTRAL
1679
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
NSC
757843
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
EVMPD
SUB08731MIG
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
DAILYMED
W8O17SJF3T
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
DRUG BANK
DB01043
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
WIKIPEDIA
MEMANTINE
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
MERCK INDEX
M7167
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY Merck Index
MESH
D008559
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
ChEMBL
CHEMBL807
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY
CHEBI
64312
Created by admin on Wed Jul 05 23:27:53 UTC 2023 , Edited by admin on Wed Jul 05 23:27:53 UTC 2023
PRIMARY