MEMANTINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H21N
Molecular Weight	179.3023
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

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 2577

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 7997	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 1470	substrate 865	substrate 1038	inhibitor 1360

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 97 OCT1 473 OCT2 582 OCT3 139	CYP1A2 892 CYP2E1 567 CYP2B6 575 CYP2A6 452 CYP2C19 830 P-gp 1223 OCT2 304

Drug as perpetrator

Target	Modality	Activity
CYP 131	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=12 Page: 12.0	no
OCT3 139	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 236 uM]
OCT1 488	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 3.7 uM]
OCT2 583	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 7.3 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 892	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2A6 452	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2B6 575	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2C19 830	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2C9 865	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2D6 1038	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2E1 567	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP3A4 1470	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
P-gp 1223	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
OCT2 304	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/9687576/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1392	inhibitor 1374 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
How to overcome resistance of influenza A viruses against adamantane derivatives.	1998 Feb	9588841
Anticonvulsants for soman-induced seizure activity.	1999 Mar-Apr	10087439
Low affinity channel blocking (uncompetitive) NMDA receptor antagonists as therapeutic agents--toward an understanding of their favorable tolerability.	2000	11026482
NMDA antagonists inhibit the development of ethanol dependence in rats.	2001 Jan-Feb	11785910
Involvement of nitric oxide in myotoxicity produced by diisopropylphosphorofluoridate (DFP)-induced muscle hyperactivity.	2002 Dec	12451448
Effect of BD 1047, a sigma1 receptor antagonist, in the animal models predictive of antipsychotic activity.	2006 Sep-Oct	17085854
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
Memantine-induced hepatitis with cholestasis in a very elderly patient.	2008 Apr 15	18413635
Effects of memantine on neuronal structure and conditioned fear in the Tg2576 mouse model of Alzheimer's disease.	2008 Dec	18418360
Memantine-induced myoclonus and delirium exacerbated by trimethoprim.	2008 Mar	18303133
Ca2+ inhibits the association of memantine with N-methyl-D-aspartate (NMDA) receptor-gated ion channels.	2008 Sep	18758084
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
Inhibition of apoptosis in human retinal pigment epithelial cells treated with benzo(e)pyrene, a toxic component of cigarette smoke.	2010 May	19959636
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

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

MEMANTINE [WHO-DD]

Common 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

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