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Record Information
Version3.6
Creation Date2012-09-06 15:16:51 UTC
Update Date2016-02-11 01:31:46 UTC
HMDB IDHMDB15177
Secondary Accession NumbersNone
Metabolite Identification
Common NameMemantine
DescriptionMemantine is an amantadine derivative with low to moderate-affinity for NMDA receptors. It is a noncompetitive NMDA receptor antagonist that binds preferentially to NMDA receptor-operated cation channels. It blocks the effects of excessive levels of glutamate that may lead to neuronal dysfunction. It is under investigation for the treatment of Alzheimer's disease, but there has been no clinical support for the prevention or slowing of disease progression.
Structure
Thumb
Synonyms
ValueSource
1,3-Dimethyl-5-adamantanamineChEBI
1-amino-3,5-DimethyladamantaneChEBI
3,5-Dimethyl-1-adamantanamineChEBI
3,5-Dimethyl-1-aminoadamantaneChEBI
3,5-dimethyltricyclo(3.3.1.1(3,7))Decan-1-amineChEBI
MemantinaChEBI
MemantinumChEBI
Chemical FormulaC12H21N
Average Molecular Weight179.3018
Monoisotopic Molecular Weight179.167399677
IUPAC Name3,5-dimethyladamantan-1-amine
Traditional Namememantine
CAS Registry Number19982-08-2
SMILES
CC12CC3CC(C)(C1)CC(N)(C3)C2
InChI Identifier
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
InChI KeyInChIKey=BUGYDGFZZOZRHP-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as cyclohexylamines. These are organic compounds containing a cyclohexylamine moiety, which consist of a cyclohexane ring attached to an amine group.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassCyclohexylamines
Sub ClassNot Available
Direct ParentCyclohexylamines
Alternative Parents
Substituents
  • Cyclohexylamine
  • Hydrocarbon derivative
  • Primary amine
  • Primary aliphatic amine
  • Amine
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External DescriptorsNot Available
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antidyskinetics
  • Antiparkinson Agents
  • Central Nervous System Agents
  • Dopamine Agents
  • Excitatory Amino Acid Antagonists
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point258 °C (hydrochloride salt)Not Available
Boiling PointNot AvailableNot Available
Water Solubility4.55e-02 g/LNot Available
LogP3.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.045 mg/mLALOGPS
logP3.31ALOGPS
logP2.07ChemAxon
logS-3.6ALOGPS
pKa (Strongest Basic)10.7ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area26.02 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity54.49 m3·mol-1ChemAxon
Polarizability21.82 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01043
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01043
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-6 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-3 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01043
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3914
KEGG Compound IDC13736
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkMemantine
NuGOwiki LinkHMDB15177
Metagene LinkHMDB15177
METLIN IDNot Available
PubChem Compound4054
PDB IDNot Available
ChEBI ID64312
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Rammes G, Rupprecht R, Ferrari U, Zieglgansberger W, Parsons CG: The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner. Neurosci Lett. 2001 Jun 22;306(1-2):81-4. [11403963 ]
  2. Rogawski MA, Wenk GL: The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev. 2003 Fall;9(3):275-308. [14530799 ]
  3. Cacabelos R, Takeda M, Winblad B: The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer's disease. Int J Geriatr Psychiatry. 1999 Jan;14(1):3-47. [10029935 ]
  4. Rogawski MA: Low affinity channel blocking (uncompetitive) NMDA receptor antagonists as therapeutic agents--toward an understanding of their favorable tolerability. Amino Acids. 2000;19(1):133-49. [11026482 ]
  5. Robinson DM, Keating GM: Memantine: a review of its use in Alzheimer's disease. Drugs. 2006;66(11):1515-34. [16906789 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular weight:
55944.565
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular weight:
56277.81
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Gene Name:
CYP2A6
Uniprot ID:
P11509
Molecular weight:
56517.005
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in ionotropic glutamate receptor activity
Specific function:
NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunits
Gene Name:
GRIN2A
Uniprot ID:
Q12879
Molecular weight:
165281.2
References
  1. Chen HS, Lipton SA: Pharmacological implications of two distinct mechanisms of interaction of memantine with N-methyl-D-aspartate-gated channels. J Pharmacol Exp Ther. 2005 Sep;314(3):961-71. Epub 2005 May 18. [15901795 ]
  2. Maler JM, Esselmann H, Wiltfang J, Kunz N, Lewczuk P, Reulbach U, Bleich S, Ruther E, Kornhuber J: Memantine inhibits ethanol-induced NMDA receptor up-regulation in rat hippocampal neurons. Brain Res. 2005 Aug 9;1052(2):156-62. [16009352 ]
  3. Bresink I, Benke TA, Collett VJ, Seal AJ, Parsons CG, Henley JM, Collingridge GL: Effects of memantine on recombinant rat NMDA receptors expressed in HEK 293 cells. Br J Pharmacol. 1996 Sep;119(2):195-204. [8886398 ]
  4. Blanpied TA, Boeckman FA, Aizenman E, Johnson JW: Trapping channel block of NMDA-activated responses by amantadine and memantine. J Neurophysiol. 1997 Jan;77(1):309-23. [9120573 ]
  5. Rogawski MA, Wenk GL: The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev. 2003 Fall;9(3):275-308. [14530799 ]
General function:
Involved in ionotropic glutamate receptor activity
Specific function:
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine
Gene Name:
GRIN2B
Uniprot ID:
Q13224
Molecular weight:
166365.9
References
  1. Kashiwagi K, Masuko T, Nguyen CD, Kuno T, Tanaka I, Igarashi K, Williams K: Channel blockers acting at N-methyl-D-aspartate receptors: differential effects of mutations in the vestibule and ion channel pore. Mol Pharmacol. 2002 Mar;61(3):533-45. [11854433 ]
  2. Nakazato E, Kato A, Watanabe S: Brain but not spinal NR2B receptor is responsible for the anti-allodynic effect of an NR2B subunit-selective antagonist CP-101,606 in a rat chronic constriction injury model. Pharmacology. 2005 Jan;73(1):8-14. Epub 2004 Sep 27. [15452358 ]
  3. Maler JM, Esselmann H, Wiltfang J, Kunz N, Lewczuk P, Reulbach U, Bleich S, Ruther E, Kornhuber J: Memantine inhibits ethanol-induced NMDA receptor up-regulation in rat hippocampal neurons. Brain Res. 2005 Aug 9;1052(2):156-62. [16009352 ]
  4. Blanpied TA, Boeckman FA, Aizenman E, Johnson JW: Trapping channel block of NMDA-activated responses by amantadine and memantine. J Neurophysiol. 1997 Jan;77(1):309-23. [9120573 ]
  5. Rogawski MA, Wenk GL: The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev. 2003 Fall;9(3):275-308. [14530799 ]
General function:
Involved in extracellular ligand-gated ion channel activity
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel
Gene Name:
HTR3A
Uniprot ID:
P46098
Molecular weight:
55279.8
References
  1. Rammes G, Rupprecht R, Ferrari U, Zieglgansberger W, Parsons CG: The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner. Neurosci Lett. 2001 Jun 22;306(1-2):81-4. [11403963 ]
General function:
Involved in ionotropic glutamate receptor activity
Specific function:
NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism
Gene Name:
GRIN3A
Uniprot ID:
Q8TCU5
Molecular weight:
125464.1
References
  1. Smothers CT, Woodward JJ: Pharmacological characterization of glycine-activated currents in HEK 293 cells expressing N-methyl-D-aspartate NR1 and NR3 subunits. J Pharmacol Exp Ther. 2007 Aug;322(2):739-48. Epub 2007 May 14. [17502428 ]
  2. Chatterton JE, Awobuluyi M, Premkumar LS, Takahashi H, Talantova M, Shin Y, Cui J, Tu S, Sevarino KA, Nakanishi N, Tong G, Lipton SA, Zhang D: Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature. 2002 Feb 14;415(6873):793-8. Epub 2002 Jan 30. [11823786 ]
  3. Schrattenholz A, Soskic V: NMDA receptors are not alone: dynamic regulation of NMDA receptor structure and function by neuregulins and transient cholesterol-rich membrane domains leads to disease-specific nuances of glutamate-signalling. Curr Top Med Chem. 2006;6(7):663-86. [16719808 ]
  4. Foster AC, Kemp JA: Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17. Epub 2005 Dec 22. [16377242 ]
  5. Rogawski MA, Wenk GL: The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev. 2003 Fall;9(3):275-308. [14530799 ]

Transporters

General function:
Involved in ion transmembrane transporter activity
Specific function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular weight:
62564.0
References
  1. Busch AE, Karbach U, Miska D, Gorboulev V, Akhoundova A, Volk C, Arndt P, Ulzheimer JC, Sonders MS, Baumann C, Waldegger S, Lang F, Koepsell H: Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998 Aug;54(2):342-52. [9687576 ]