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

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 123 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9120573	Antagonist 2737

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 8307	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 1670	substrate 985	substrate 1168	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 107 OCT1 498 OCT2 630 OCT3 143	CYP1A2 1013 CYP2E1 633 CYP2B6 648 CYP2A6 510 CYP2C19 955 P-gp 1491 OCT2 336

Drug as perpetrator

Target	Modality	Activity
CYP 143	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=12 Page: 12.0	no
OCT3 143	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 236 uM]
OCT1 513	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 3.7 uM]
OCT2 631	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 7.3 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1013	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2A6 510	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2B6 648	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2C19 955	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2C9 985	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2D6 1168	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2E1 633	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP3A4 1670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
P-gp 1491	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
OCT2 336	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/9687576/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 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
Methyl parathion acute toxicity: prophylaxis and therapy with memantine and atropine.	1990 May-Jun	2241428
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
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
Low affinity channel blocking (uncompetitive) NMDA receptor antagonists as therapeutic agents--toward an understanding of their favorable tolerability.	2000	11026482
Prevention of cocaine-induced convulsions and lethality in mice: effectiveness of targeting different sites on the NMDA receptor complex.	2000 Jan 28	10698007
Effects of the NMDA receptor channel blockers memantine and MRZ 2/579 on morphine withdrawal-facilitated aggression in mice.	2000 May	10867961
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
Are neuronal nicotinic receptors a target for antiepileptic drug development? Studies in different seizure models in mice and rats.	2003 Apr 11	12679146
The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease.	2003 Fall	14530799
Mechanisms intrinsic to 5-HT2B receptor-induced potentiation of NMDA receptor responses in frog motoneurones.	2004 Oct	15339859
Exacerbation of Lewy bodies dementia due to memantine.	2005 Dec	16340086
Memantine alleviates toxicity induced by dichlorvos in rats.	2005 Mar	15824473
A comparison of the predictive therapeutic and undesired side-effects of the NMDA receptor antagonist, memantine, in mice.	2005 May	15864070
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	16161183
Exacerbation of myoclonus by memantine in a patient with Alzheimer disease.	2007 Aug	17632233
A retrospective study of memantine in children and adolescents with pervasive developmental disorders.	2007 Mar	17016714
Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability.	2007 May	17690064
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
Effects of memantine on neuronal structure and conditioned fear in the Tg2576 mouse model of Alzheimer's disease.	2008 Dec	18418360
Memantine and NMDA antagonism for chronic migraine: a potentially novel therapeutic approach?	2008 Feb	18194287
Memantine prevents the cognitive impairment induced by 3,4-methylenedioxymethamphetamine in rats.	2008 Jul 28	18582864
Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer's disease: a pooled analysis of 3 studies.	2008 Mar	18294023
The attenuating effect of memantine on staurosporine-, salsolinol- and doxorubicin-induced apoptosis in human neuroblastoma SH-SY5Y cells.	2008 Mar-Apr	17996985
Does memantine induce bradycardia? A study in the French PharmacoVigilance Database.	2008 Sep	18500725
Memanti-nium chloride 0.1-hydrate.	2009 Aug 19	21577595
Memantine dosing in patients with dementia.	2009 Feb	19155749
Role of N-methyl-D-aspartate receptors in polychlorinated biphenyl mediated neurotoxicity.	2009 Jan 10	19022367
Treatment of acquired periodic alternating nystagmus with memantine: a case report.	2009 Mar-Apr	19512963
[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
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
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	22784018
Glial activation and post-synaptic neurotoxicity: the key events in Streptozotocin (ICV) induced memory impairment in rats.	2014 Feb	24333387

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.

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