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

Molecular Formula C12H21N
Molecular Weight 179.3018
Charge 0
Count
Stereochemistry MIXED
Additional Stereochemistry No
Defined Stereocenters 0 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

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
[Memantine and neurogenic bladder disorders within the bounds of spastic conditions].
1982
Susceptibility of primary human glial fibrillary acidic protein-positive brain cells to human immunodeficiency virus infection in vitro: anti-HIV activity of memantine.
1991 Jan
gp120 of HIV-1 induces apoptosis in rat cortical cell cultures: prevention by memantine.
1992 Jul 1
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
Anticonvulsant efficacy of N-methyl-D-aspartate antagonists against convulsions induced by cocaine.
1999 May
Prevention of cocaine-induced convulsions and lethality in mice: effectiveness of targeting different sites on the NMDA receptor complex.
2000 Jan 28
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
A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500).
2002 Nov
Exacerbation of Lewy bodies dementia due to memantine.
2005 Dec
Memantine alleviates toxicity induced by dichlorvos in rats.
2005 Mar
Memantine: a review of its use in Alzheimer's disease.
2006
Exacerbation of myoclonus by memantine in a patient with Alzheimer disease.
2007 Aug
Safety and tolerability of once-daily versus twice-daily memantine: a randomised, double-blind study in moderate to severe Alzheimer's disease.
2007 Mar
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
Memantine-induced hepatitis with cholestasis in a very elderly patient.
2008 Apr 15
Memantine and NMDA antagonism for chronic migraine: a potentially novel therapeutic approach?
2008 Feb
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
Does memantine induce bradycardia? A study in the French PharmacoVigilance Database.
2008 Sep
Memanti-nium chloride 0.1-hydrate.
2009 Aug 19
Role of N-methyl-D-aspartate receptors in polychlorinated biphenyl mediated neurotoxicity.
2009 Jan 10
Characteristic effects of anti-dementia drugs on rat sleep patterns.
2009 Mar
[Effects of electroacupuncture on expression of Abeta positive cells of the hippocampus and SOD activity in rats with streptozocin-Alzheimer's disease].
2010 Dec
Memantine ameliorates scopolamine-induced amnesia in chicks trained on taste-avoidance learning.
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
Memantine prevents aluminum-induced cognitive deficit in rats.
2011 Nov 20
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.
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:27:53 UTC 2023
Edited
by admin
on Wed Jul 05 23:27:53 UTC 2023
Record UNII
W8O17SJF3T
Record Status Validated (UNII)
Record Version
  • Download
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
Related Record Type Details
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
TARGET -> AGONIST
ALZHEIMERS DISEASE DRUG ANTAGONIZING NMDA RECEPTOR, ANTAGONISM OF .ALPHA.7 NACHR IS A SIDE PATHWAY.
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
BINDING
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
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METABOLITE INACTIVE -> PARENT
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC Elimination
PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC