MEMANTINE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H21N.ClH
Molecular Weight	215.763
Optical Activity	NONE
Defined Stereocenters	0 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=LDDHMLJTFXJGPI-UHFFFAOYSA-N

InChI=1S/C12H21N.ClH/c1-10-3-9-4-11(2,6-10)8-12(13,5-9)7-10;/h9H,3-8,13H2,1-2H3;1H

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 125 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9120573	Antagonist 2778

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 8429	NAMENDA Approved Use Namenda (memantine hydrochloride) is indicated for the treatment of moderate to severe dementia of the Alzheimer's type. Launch Date 2003

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 1737	substrate 1037	substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 111 OCT1 512 OCT2 647 OCT3 150	CYP1A2 1054 CYP2E1 667 CYP2B6 664 CYP2A6 543 CYP2C19 991 P-gp 1537 OCT2 355

Drug as perpetrator

Target	Modality	Activity
CYP 147	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=12 Page: 12.0	no
OCT3 150	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 236 uM]
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 3.7 uM]
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 7.3 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-487_Namenda_Bioeqr_P1.pdf#page=37 Page: 37.0	no
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9687576/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 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
Methyl parathion acute toxicity: prophylaxis and therapy with memantine and atropine.	1990 May-Jun	2241428
gp120 of HIV-1 induces apoptosis in rat cortical cell cultures: prevention by memantine.	1992 Jul 1	1426020
The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer's disease.	1999 Jan	10029935
Anticonvulsants for soman-induced seizure activity.	1999 Mar-Apr	10087439
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
Synergistic neurotoxicity by human immunodeficiency virus proteins Tat and gp120: protection by memantine.	2000 Feb	10665489
Prevention of cocaine-induced convulsions and lethality in mice: effectiveness of targeting different sites on the NMDA receptor complex.	2000 Jan 28	10698007
[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	10834088
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
The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease.	2003 Fall	14530799
The ability of new non-competitive glutamate receptor blockers to weaken motor disorders in animals.	2003 Mar	12762595
Development of subtle psychotic symptoms with memantine: a case report.	2005 May	15889961
A comparison of the predictive therapeutic and undesired side-effects of the NMDA receptor antagonist, memantine, in mice.	2005 May	15864070
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
[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
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
Galantamine-induced pisa syndrome: memantine as an alternative.	2008 Jun	18506913
Memantine-induced myoclonus and delirium exacerbated by trimethoprim.	2008 Mar	18303133
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
Ca2+ inhibits the association of memantine with N-methyl-D-aspartate (NMDA) receptor-gated ion channels.	2008 Sep	18758084
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
NMDA antagonist memantine improves levodopa-induced dyskinesias and "on-off" phenomena in Parkinson's disease.	2010 Mar 15	20014061
Inhibition of apoptosis in human retinal pigment epithelial cells treated with benzo(e)pyrene, a toxic component of cigarette smoke.	2010 May	19959636
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
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 HYDROCHLORIDE

Official Name

English

MEMANTINE HCL

Common Name

English

Memantine hydrochloride [WHO-DD]

Common Name

English

ACRESCENT

Brand Name

English

EBIXA

Brand Name

English

MEMANTINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

AUXURA

Brand Name

English

NAMZARIC COMPONENT MEMANTINE HYDROCHLORIDE

Brand Name

English

3,5-DIMETHYLTRICYCLO(3.3.1.1(SUP 3,7))DECAN-1-AMINE HYDROCHLORIDE

Systematic Name

English

NAMENDA

Brand Name

English

MEMANTINE RATIOPHARM

Brand Name

English

MEMANTINE HYDROCHLORIDE [JAN]

Common Name

English

1-AMINO-3,5-DIMETHYLADAMANTANE HYDROCHLORIDE

Systematic Name

English

MARIXINO

Brand Name

English

MEMANTINE MYLAN

Brand Name

English

MEMANTINE HYDROCHLORIDE [USP-RS]

Common Name

English

MEMANTINE MERZ

Brand Name

English

MEMARY

Brand Name

English

MEMANTINE HYDROCHLORIDE [MI]

Common Name

English

NSC-102290

Code

English

TRICYCLO(3.3.1.1(SUP 3,7))DECAN-1-AMINE, 3,5-DIMETHYL-, HYDROCHLORIDE

Common Name

English

MEMANTINE HYDROCHLORIDE [MART.]

Common Name

English

SUN-Y7017

Code

English

MEMANTINE HYDROCHLORIDE COMPONENT OF NAMZARIC

Brand Name

English

MEMANTINE HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

3,5-DIMETHYL-1-ADAMANTANAMINE HYDROCHLORIDE

Systematic Name

English

BALAXUR

Brand Name

English

AKATINOL

Brand Name

English

MEMANTINE HYDROCHLORIDE [USAN]

Common Name

English

MEMANTINE LEK

Brand Name

English

FP-01

Code

English

MEMANTINE HYDROCHLORIDE [EMA EPAR]

Common Name

English

MEMANTINE ACCORD

Brand Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

EBIXA (AUTHORIZED: ALZHEIMER DISEASE)