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
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
Anticonvulsants for soman-induced seizure activity.	1999 Mar-Apr	10087439
Effects of the NMDA receptor channel blockers memantine and MRZ 2/579 on morphine withdrawal-facilitated aggression in mice.	2000 May	10867961
Are neuronal nicotinic receptors a target for antiepileptic drug development? Studies in different seizure models in mice and rats.	2003 Apr 11	12679146
Memantine attenuates the increase in striatal preproenkephalin mRNA expression and development of haloperidol-induced persistent oral dyskinesias in rats.	2003 Dec 24	14642644
The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease.	2003 Fall	14530799
New platinum(IV) complex with adamantylamine ligand as a promising anti-cancer drug: comparison of in vitro cytotoxic potential towards A2780/cisR cisplatin-resistant cell line within homologous series of platinum(IV) complexes.	2004 Jun	15166629
Mechanisms intrinsic to 5-HT2B receptor-induced potentiation of NMDA receptor responses in frog motoneurones.	2004 Oct	15339859
Memantine alleviates toxicity induced by dichlorvos in rats.	2005 Mar	15824473
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
Memantine: a review of its use in Alzheimer's disease.	2006	16906789
Effect of BD 1047, a sigma1 receptor antagonist, in the animal models predictive of antipsychotic activity.	2006 Sep-Oct	17085854
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
Effects of memantine on neuronal structure and conditioned fear in the Tg2576 mouse model of Alzheimer's disease.	2008 Dec	18418360
Galantamine-induced pisa syndrome: memantine as an alternative.	2008 Jun	18506913
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
NMDA antagonist memantine improves levodopa-induced dyskinesias and "on-off" phenomena in Parkinson's disease.	2010 Mar 15	20014061
Memantine ameliorates scopolamine-induced amnesia in chicks trained on taste-avoidance learning.	2010 May	20170739
Inhibition of apoptosis in human retinal pigment epithelial cells treated with benzo(e)pyrene, a toxic component of cigarette smoke.	2010 May	19959636
Memantine in patients with moderate to severe Alzheimer's disease: meta-analyses using realistic definitions of response.	2014	24107324
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)