MEMANTINE

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 Search

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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021487s010s012s014,021627s008lbl.pdf
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate [NMDA] receptor 124 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9120573	Antagonist 2760

Conditions

Condition	Modality	Targets	Highest Phase	Product
Moderate to severe dementia of the Alzheimer’s type 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021487s010s012s014,021627s008lbl.pdf	Primary		Approved 8360	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

C_max

Value	Dose	Analyte	Population
25.34 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18498913	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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18498913	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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18498913	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

Value	Dose	Analyte	Population
1853 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18498913	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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18498913	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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18498913	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

T_1/2

Value	Dose	Analyte	Population
62 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18498913	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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18498913	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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18498913	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

Dose	Population	Adverse events
400 mg single, oral Highest studied dose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf

AEs

AE	Significance	Dose	Population
Loss of consciousness	1 patient	400 mg single, oral Highest studied dose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf
Psychosis	1 patient	400 mg single, oral Highest studied dose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf
Restlessness	1 patient	400 mg single, oral Highest studied dose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf
Somnolence	1 patient	400 mg single, oral Highest studied dose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf
Stupor	1 patient	400 mg single, oral Highest studied dose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf
Visual hallucinations	1 patient	400 mg single, oral Highest studied dose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021487lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709	substrate 1010	substrate 1193	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 110 OCT1 506 OCT2 638 OCT3 149	CYP1A2 1032 CYP2E1 648 CYP2B6 660 CYP2A6 523 CYP2C19 985 P-gp 1527 OCT2 348

Drug as perpetrator

Target	Modality	Activity
CYP 146	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=12 Page: 12.0	no
OCT3 149	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 236 uM]
OCT1 523	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 3.7 uM]
OCT2 639	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 7.3 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1032	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2A6 523	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2B6 660	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2C19 985	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2C9 1010	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2D6 1193	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2E1 648	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP3A4 1709	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
P-gp 1527	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
OCT2 348	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9687576/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Pharmr_P1.pdf#page=16 Page: 16.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:64312	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:64312
ChemicalBook	CB7436657	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7436657
MolPort	MolPort-002-041-858	https://www.molport.com/shop/molecule-link/MolPort-002-041-858
eMolecules	902095	https://www.emolecules.com/cgi-bin/more?vid=902095

PubMed

Title	Date	PubMed

[Memantine and neurogenic bladder disorders within the bounds of spastic conditions].	1982	6891227
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	1707644
gp120 of HIV-1 induces apoptosis in rat cortical cell cultures: prevention by memantine.	1992 Jul 1	1426020
Inhibition by memantine of the development of persistent oral dyskinesias induced by long-term haloperidol treatment of rats.	1996 Oct	8904651
How to overcome resistance of influenza A viruses against adamantane derivatives.	1998 Feb	9588841
Anticonvulsant efficacy of N-methyl-D-aspartate antagonists against convulsions induced by cocaine.	1999 May	10215643
Prevention of cocaine-induced convulsions and lethality in mice: effectiveness of targeting different sites on the NMDA receptor complex.	2000 Jan 28	10698007
Uncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptors alter the mRNA expression of proteins associated with the NMDA receptor complex.	2001 Feb	11169168
NMDA antagonists inhibit the development of ethanol dependence in rats.	2001 Jan-Feb	11785910
A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500).	2002 Nov	12409683
Exacerbation of Lewy bodies dementia due to memantine.	2005 Dec	16340086
Memantine alleviates toxicity induced by dichlorvos in rats.	2005 Mar	15824473
Memantine: a review of its use in Alzheimer's disease.	2006	16906789
Exacerbation of myoclonus by memantine in a patient with Alzheimer disease.	2007 Aug	17632233
Safety and tolerability of once-daily versus twice-daily memantine: a randomised, double-blind study in moderate to severe Alzheimer's disease.	2007 Mar	17243195
Visual hallucinations and agitation in Alzheimer's disease due to memantine: report of three cases.	2007 May	17030587
[Therapy of Alzheimer's disease: current status and future development].	2008	18826870
Memantine-induced hepatitis with cholestasis in a very elderly patient.	2008 Apr 15	18413635
Memantine and NMDA antagonism for chronic migraine: a potentially novel therapeutic approach?	2008 Feb	18194287
Methylmercury increases N-methyl-D-aspartate receptors on human SH-SY 5Y neuroblastoma cells leading to neurotoxicity.	2008 Jul 30	18597911
Galantamine-induced pisa syndrome: memantine as an alternative.	2008 Jun	18506913
Memantine-induced myoclonus and delirium exacerbated by trimethoprim.	2008 Mar	18303133
Does memantine induce bradycardia? A study in the French PharmacoVigilance Database.	2008 Sep	18500725
Memanti-nium chloride 0.1-hydrate.	2009 Aug 19	21577595
Role of N-methyl-D-aspartate receptors in polychlorinated biphenyl mediated neurotoxicity.	2009 Jan 10	19022367
Characteristic effects of anti-dementia drugs on rat sleep patterns.	2009 Mar	19305123
[Effects of electroacupuncture on expression of Abeta positive cells of the hippocampus and SOD activity in rats with streptozocin-Alzheimer's disease].	2010 Dec	21290839
Memantine ameliorates scopolamine-induced amnesia in chicks trained on taste-avoidance learning.	2010 May	20170739
Protective effects of memantine and epicatechin on catechol-induced toxicity on Müller cells in vitro.	2010 May 27	20347921
Memantine is a useful drug to prevent the spatial and non-spatial memory deficits induced by methamphetamine in rats.	2010 Nov	20553881
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	21179320
Memantine prevents aluminum-induced cognitive deficit in rats.	2011 Nov 20	21741993
Memantine in patients with moderate to severe Alzheimer's disease: meta-analyses using realistic definitions of response.	2014	24107324

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

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Name

Type

Language

MEMANTINE

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