Details of the Drug

General Information of Drug (ID: DMD9WSC)

• Drug Name: Memantine
• Synonyms: Memantine ER; Namenda XR; Memantine (extended release); Memantine (extended release), Forest

Indication

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Approved	[1]
Asperger syndrome	N.A.	Approved	[2]
Glioblastoma	2A00	Approved	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 179.3
  Logarithm of the Partition Coefficient (xlogp); 3.3
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 1
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 3-7 h []
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
  Bioavailability: 99% of drug becomes completely available to its intended biological destination(s) [4]
  Elimination: Approximately 48% of administered memantine is excreted unchanged in urine []
  Half-life: The concentration or amount of drug in body reduced by one-half in 60 - 100 hours []
  Metabolism: The drug is metabolized via the liver []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1.324 micromolar/kg/day [5]
  Vd: The volume of distribution (Vd) of drug is 9-11 L/kg []
• Chemical Identifiers:
  Formula: C12H21N
  IUPAC Name: 3,5-dimethyladamantan-1-amine
  Canonical SMILES: CC12CC3CC(C1)(CC(C3)(C2)N)C
  InChI: 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
  InChIKey: BUGYDGFZZOZRHP-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4054
  ChEBI ID: CHEBI:64312
  CAS Number: 19982-08-2
  DrugBank ID: DB01043
  TTD ID: D01JEU
  VARIDT ID: DR00023
  INTEDE ID: DR2292
  ACDINA ID: D00395
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
N-methyl-D-aspartate receptor (NMDAR)	TT9IK2Z	NOUNIPROTAC	Modulator	[6]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[7]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[8]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[8]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Gene/Protein Processing	[8]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[8]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Gene/Protein Processing	[8]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Gene/Protein Processing	[8]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Gene/Protein Processing	[8]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Gene/Protein Processing	[8]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Memantine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Mepyramine	DMB4SFH	Moderate	Additive anticholinergic effects by the combination of Memantine and Mepyramine.	Allergic/hypersensitivity disorder [4A80-4A8Z]	[9]
Phenyltoloxamine	DMKAEQW	Moderate	Additive anticholinergic effects by the combination of Memantine and Phenyltoloxamine.	Allergic/hypersensitivity disorder [4A80-4A8Z]	[9]
Desipramine	DMT2FDC	Moderate	Additive anticholinergic effects by the combination of Memantine and Desipramine.	Attention deficit hyperactivity disorder [6A05]	[10]
Cariprazine	DMJYDVK	Moderate	Additive anticholinergic effects by the combination of Memantine and Cariprazine.	Bipolar disorder [6A60]	[10]
OPC-34712	DMHG57U	Moderate	Additive anticholinergic effects by the combination of Memantine and OPC-34712.	Depression [6A70-6A7Z]	[10]
Clomipramine	DMINRKW	Moderate	Additive anticholinergic effects by the combination of Memantine and Clomipramine.	Depression [6A70-6A7Z]	[10]
Doxepin	DMPI98T	Moderate	Additive anticholinergic effects by the combination of Memantine and Doxepin.	Depression [6A70-6A7Z]	[10]
Mepenzolate	DM8YU2F	Moderate	Additive anticholinergic effects by the combination of Memantine and Mepenzolate.	Digestive system disease [DE2Z]	[10]
Oxybutynine	DMJPBAX	Moderate	Additive anticholinergic effects by the combination of Memantine and Oxybutynine.	Discovery agent [N.A.]	[10]
Diphenhydramine	DMKQTBA	Moderate	Additive anticholinergic effects by the combination of Memantine and Diphenhydramine.	Episodic vestibular syndrome [AB31]	[10]
Solifenacin	DMG592Q	Moderate	Additive anticholinergic effects by the combination of Memantine and Solifenacin.	Functional bladder disorder [GC50]	[10]
Belladonna	DM2RBWK	Moderate	Additive anticholinergic effects by the combination of Memantine and Belladonna.	Infectious gastroenteritis/colitis [1A40]	[10]
ITI-007	DMUQ1DO	Moderate	Additive anticholinergic effects by the combination of Memantine and ITI-007.	Insomnia [7A00-7A0Z]	[10]
Phenindamine	DMDTC7R	Moderate	Additive anticholinergic effects by the combination of Memantine and Phenindamine.	Nasopharyngitis [CA00]	[10]
Promethazine	DM6I5GR	Moderate	Additive anticholinergic effects by the combination of Memantine and Promethazine.	Nausea/vomiting [MD90]	[10]
Cyclizine	DM9G7BS	Moderate	Additive anticholinergic effects by the combination of Memantine and Cyclizine.	Nausea/vomiting [MD90]	[10]
Flavoxate	DMKV4NL	Moderate	Additive anticholinergic effects by the combination of Memantine and Flavoxate.	Pain [MG30-MG3Z]	[10]
Pergolide	DM14MAE	Minor	Additive dopaminergic effects by the combination of Memantine and Pergolide.	Parkinsonism [8A00]	[11]
Opicapone	DM1BKA6	Minor	Additive dopaminergic effects by the combination of Memantine and Opicapone.	Parkinsonism [8A00]	[11]
Levodopa	DMN3E57	Minor	Additive dopaminergic effects by the combination of Memantine and Levodopa.	Parkinsonism [8A00]	[11]
Bromocriptine	DMVE3TK	Minor	Additive dopaminergic effects by the combination of Memantine and Bromocriptine.	Parkinsonism [8A00]	[11]
Orphenadrine	DMW542E	Moderate	Additive anticholinergic effects by the combination of Memantine and Orphenadrine.	Parkinsonism [8A00]	[10]
Methylscopolamine	DM5VWOB	Moderate	Additive anticholinergic effects by the combination of Memantine and Methylscopolamine.	Peptic ulcer [DA61]	[10]
Levomepromazine	DMIKFEL	Moderate	Additive anticholinergic effects by the combination of Memantine and Levomepromazine.	Psychotic disorder [6A20-6A25]	[10]
Neupro	DMHEAB1	Minor	Additive dopaminergic effects by the combination of Memantine and Neupro.	Restless legs syndrome [7A80]	[11]
Quetiapine	DM1N62C	Moderate	Additive anticholinergic effects by the combination of Memantine and Quetiapine.	Schizophrenia [6A20]	[10]
Aripiprazole	DM3NUMH	Moderate	Additive anticholinergic effects by the combination of Memantine and Aripiprazole.	Schizophrenia [6A20]	[10]
Iloperidone	DM6AUFY	Moderate	Additive anticholinergic effects by the combination of Memantine and Iloperidone.	Schizophrenia [6A20]	[10]
Paliperidone	DM7NPJS	Moderate	Additive anticholinergic effects by the combination of Memantine and Paliperidone.	Schizophrenia [6A20]	[10]
Molindone	DMAH70G	Moderate	Additive anticholinergic effects by the combination of Memantine and Molindone.	Schizophrenia [6A20]	[10]
Thiothixene	DMDINC4	Moderate	Additive anticholinergic effects by the combination of Memantine and Thiothixene.	Schizophrenia [6A20]	[10]
Asenapine	DMSQZE2	Moderate	Additive anticholinergic effects by the combination of Memantine and Asenapine.	Schizophrenia [6A20]	[10]
Pimozide	DMW83TP	Moderate	Additive anticholinergic effects by the combination of Memantine and Pimozide.	Schizophrenia [6A20]	[10]
Chlorpheniramine	DM5URA2	Moderate	Additive anticholinergic effects by the combination of Memantine and Chlorpheniramine.	Vasomotor/allergic rhinitis [CA08]	[10]
Trimeprazine	DMEMV9D	Moderate	Additive anticholinergic effects by the combination of Memantine and Trimeprazine.	Vasomotor/allergic rhinitis [CA08]	[9]
Acrivastine	DMTIGA0	Moderate	Additive anticholinergic effects by the combination of Memantine and Acrivastine.	Vasomotor/allergic rhinitis [CA08]	[10]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
FD&C blue no. 2	E00446	2723854	Colorant
Quinoline yellow WS	E00309	24671	Colorant
Sodium stearyl fumarate	E00545	23665634	lubricant
Sunset yellow FCF	E00255	17730	Colorant
Ammonia	E00007	222	Alkalizing agent
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Brushite	E00392	104805	Diluent
Carmellose sodium	E00625	Not Available	Disintegrant
Crospovidone	E00626	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Hypromellose	E00634	Not Available	Coating agent
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 400	E00653	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 6000	E00655	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Saccharose	E00091	5988	Binding agent; Coating agent; Cryoprotectant; Diluent; Flavoring agent; Suspending agent; Viscosity-controlling agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
Vinylpyrrolidone	E00668	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Memantine 5 mg tablet	5 mg	Oral Tablet	Oral
Memantine 10 mg tablet	10 mg	Oral Tablet	Oral
Memantine 14 mg capsule	14 mg	24 HR Extended Release Oral Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4253).
• [2] Memantine FDA Label
• [3] BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
• [4] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [5] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [6] The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidence. Int J Geriatr Psychiatry. 2003 Sep;18(Suppl 1):S23-32.
• [7] Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998 Aug;54(2):342-52.
• [8] Memantine induces apoptosis and inhibits cell cycle progression in LNCaP prostate cancer cells. Hum Exp Toxicol. 2018 Sep;37(9):953-958. doi: 10.1177/0960327117747025. Epub 2017 Dec 11.
• [9] Kulik AV, Wilbur R "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982): 75-82. [PMID: 7202232]
• [10] Cohen MA, Alfonso CA, Mosquera M. Development of urinary retention during treatment with clozapine and meclizine [published correction appears in Am J Psychiatry 1994 Jun;151(6):952]. Am J Psychiatry. 1994;151(4):619-620. [PMID: 8147469]
• [11] Cerner Multum, Inc. "UK Summary of Product Characteristics.".