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Record Information
Version2.0
Creation Date2009-07-05 03:00:16 UTC
Update Date2014-12-24 20:25:42 UTC
Accession NumberT3D2560
Identification
Common NameAmantadine
ClassSmall Molecule
DescriptionAn antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [PubChem]
Compound Type
  • Amine
  • Analgesic, Non-Narcotic
  • Antiparkinson Agent
  • Antiviral Agent
  • Dopamine Agent
  • Drug
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1-adamantanamine
1-adamantylamine
1-Aminoadamantane
Adamantamine
Adamantanamine
Adamantylamine
Amantadina
Amantadine Base
Amantadine HCL
Amantadine Hydrochloride
Amantadinum
Amantidine
Aminoadamantane
Endantadine
PK-Merz
Symadine
Symmetrel
Tricyclo[3.3.1.1(3,7)]decan-1-amine
Tricyclo[3.3.1.1(3,7)]decan-1-ylamine
Tricyclo[3.3.1.1(3,7)]decane-1-amine
Viregyt
Virosol
Chemical FormulaC10H17N
Average Molecular Mass151.249 g/mol
Monoisotopic Mass151.136 g/mol
CAS Registry Number768-94-5
IUPAC Nameadamantan-1-amine
Traditional Nameamantadine
SMILESNC12CC3CC(CC(C3)C1)C2
InChI IdentifierInChI=1S/C10H17N/c11-10-4-7-1-8(5-10)3-9(2-7)6-10/h7-9H,1-6,11H2
InChI KeyInChIKey=DKNWSYNQZKUICI-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as monoalkylamines. These are organic compounds containing an primary aliphatic amine group.
KingdomOrganic compounds
Super ClassOrganic nitrogen compounds
ClassOrganonitrogen compounds
Sub ClassAmines
Direct ParentMonoalkylamines
Alternative Parents
Substituents
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Primary aliphatic amine
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceHexakistetrahedral crystals by sublimation (3).
Experimental Properties
PropertyValue
Melting Point180-192°C
Boiling PointNot Available
Solubility6290 mg/L (freely soluble)
LogP2.44
Predicted Properties
PropertyValueSource
Water Solubility0.085 g/LALOGPS
logP2.53ALOGPS
logP1.47ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)10.71ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area26.02 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity45.54 m³·mol⁻¹ChemAxon
Polarizability17.92 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-014i-1910000000-c4908efe87e5cdf2ba74JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-014i-1910000000-8b7366cc494bf757bb81JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-01b9-6910000000-e6fd5b29f51169a772e5JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-014i-1910000000-c4908efe87e5cdf2ba74JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-014i-1910000000-8b7366cc494bf757bb81JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-01b9-6910000000-e6fd5b29f51169a772e5JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udi-0900000000-ffe93d952abd2a39e06eJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0f79-0900000000-b3511c6e5de6fce544c6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0f79-0900000000-ca740a06e33d4850b211JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-0900000000-f1084780a2940c5afd1bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-0900000000-a083f7fdcbb679c2996aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-2900000000-496b35f0cfba5aa930edJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-7900000000-e37809d5efe023b0382dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0udi-0900000000-1a8aac6647f0187ebdf9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-000i-0900000000-88a4152a7398da21333cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-000i-1900000000-76e73b05fc9ac0bdc170JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-002u-9600000000-048cdcfd022184f574b6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-004l-9000000000-8bc5ffed5487b0edffafJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0900000000-4aa7b04aaac47d693e8dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udr-0900000000-815d4b207b027466d755JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-000i-0900000000-7ce8af9197b4d35ecffdJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-000i-0900000000-278de51184b1c34ed88fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-000i-0900000000-1a9620db53d99baf9c05JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-000i-0900000000-1a9620db53d99baf9c05JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0f79-1900000000-f49f767b2078c543faadJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udr-0900000000-9de5310f392d5fea9404JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udr-0900000000-8549fa2798ea74b6bfe9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-0900000000-1bbfc183d3445dfb5be9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0900000000-1da79c1934401c0e75b1JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-0900000000-500c2b80938b31be9d7cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0udi-0900000000-6af1e4d2eb8132df1cf9JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0006-9100000000-44ff981fd5fa6c48df97JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureInhalation. Amantadine is well absorbed orally from the gastrointestinal tract.
Mechanism of ToxicityThe mechanism of its antiparkinsonic effect is not fully understood, but it appears to be releasing dopamine from the nerve endings of the brain cells, together with stimulation of norepinephrine response. It also has NMDA receptor antagonistic effects. The antiviral mechanism seems to be unrelated. The drug interferes with a viral protein, M2 (an ion channel), which is needed for the viral particle to become "uncoated" once it is taken inside the cell by endocytosis.
MetabolismNo appreciable metabolism, although negligible amounts of an acetyl metabolite have been identified. Amantadine is well absorbed orally from the gastrointestinal tract. The mechanism of its antiparkinsonic effect is not fully understood, but it appears to be releasing dopamine from the nerve endings of the brain cells, together with stimulation of norepinephrine response. The antiviral mechanism seems to be unrelated. The drug interferes with a viral protein, M2 (an ion channel), which is needed for the viral particle to become "uncoated" once it is taken inside the cell by endocytosis. Metabolites are excreted in the urine (1). Route of Elimination: It is primarily excreted unchanged in the urine by glomerular filtration and tubular secretion. Half Life: Mean half-lives ranged from 10 to 14 hours, however renal function impairment causes a severe increase in half life to 7 to 10 days.
Toxicity ValuesLD50: 800 mg/kg (Oral, Rat) LD50: 700 mg/kg (Oral, Mouse)
Lethal DoseThe lowest reported acute lethal dose was 2 grams.
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the chemoprophylaxis, prophylaxis, and treatment of signs and symptoms of infection caused by various strains of influenza A virus. Also for the treatment of parkinsonism and drug-induced extrapyramidal reactions (1).
Minimum Risk LevelNot Available
Health EffectsAcute overdosage of amantadine has resulted in cardiac dysfunction (e.g., arrhythmia, tachycardia, hypertension); pulmonary edema and respiratory distress (including adult respiratory distress syndrome); renal dysfunction (e.g., increased BUN, decreased creatinine clearance, renal insufficiency); or CNS toxicity (e.g., insomnia, anxiety, psychotic reactions, lethargy, somnolence, coma). Hyperthermia also has occurred with amantadine overdosage. In addition, seizures may be exacerbated in patients with a history of a seizure disorder (2).
SymptomsDeaths have been reported from overdose with amantadine. The lowest reported acute lethal dose was 2 grams. Drug overdose has resulted in cardiac, respiratory, renal or central nervous system toxicity. Cardiac dysfunction includes arrhythmia, tachycardia and hypertension. Pulmonary edema and respiratory distress (including ARDS) have been reported. Renal dysfunction including increased BUN, decreased creatinine clearance and renal insufficiency can occur. Central nervous system effects that have been reported include insomnia, anxiety, aggressive behavior, hypertonia, hyperkinesia, tremor, confusion, disorientation, depersonalization, fear, delirium, hallucination, psychotic reactions, lethargy, somnolence and coma. Seizures may be exacerbated in patients with prior history of seizure disorders. Hyperthermia has also been observed in cases where a drug overdose has occurred.
TreatmentThere is no specific antidote for an overdose of Amantadine. However, slowly administered intravenous physostigmine in 1 and 2 mg doses in an adult2 at 1- to 2-hour intervals and 0.5 mg doses in a child3 at 5- to 10-minute intervals up to a maximum of 2 mg/hour have been reported to be effective in the control of central nervous system toxicity caused by amantadine hydrochloride. For acute overdosing, general supportive measures should be employed along with immediate gastric lavage or induction of emesis. Fluids should be forced, and if necessary, given intravenously. The pH of the urine has been reported to influence the excretion rate of Amantadine. (5)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00915
HMDB IDHMDB15051
PubChem Compound ID2130
ChEMBL IDCHEMBL660
ChemSpider ID2045
KEGG IDC06818
UniProt IDNot Available
OMIM ID
ChEBI ID2618
BioCyc IDNot Available
CTD IDNot Available
Stitch IDAmantadine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAmantadine
References
Synthesis Reference

Haaf, W.; U.S. Patent 3,152,180; October 6, 1964; assigned to Studiengesellschaft Kohle mbH, Germany.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Segura-Aguilar J: Peroxidase activity of liver microsomal vitamin D 25-hydroxylase and cytochrome P450 1A2 catalyzes 25-hydroxylation of vitamin D3 and oxidation of dopamine to aminochrome. Biochem Mol Med. 1996 Jun;58(1):122-9. [8809353 ]
  3. Budavari, S (ed) (1989). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc.
  4. McEvoy GK (ed) (2005). American Hospital Formulary Service - Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc.
  5. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

General Function:
Protein phosphatase 2a binding
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 (By similarity).
Gene Name:
GRIN3A
Uniprot ID:
Q8TCU5
Molecular Weight:
125464.07 Da
References
  1. Blanpied TA, Clarke RJ, Johnson JW: Amantadine inhibits NMDA receptors by accelerating channel closure during channel block. J Neurosci. 2005 Mar 30;25(13):3312-22. [15800186 ]
  2. Hesselink MB, De Boer AG, Breimer DD, Danysz W: Adaptations of NMDA and dopamine D2, but not of muscarinic receptors following 14 days administration of uncompetitive NMDA receptor antagonists. J Neural Transm. 1999;106(5-6):409-21. [10443547 ]
General Function:
Monovalent cation:proton antiporter activity
Specific Function:
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:
SLC47A1
Uniprot ID:
Q96FL8
Molecular Weight:
61921.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5037.8 uMNot AvailableBindingDB 50033369
References
  1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
General Function:
Quaternary ammonium group 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:
62579.99 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5023 uMNot AvailableBindingDB 50033369
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 ]
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
DRD1
Uniprot ID:
P21728
Molecular Weight:
49292.765 Da
General Function:
Potassium channel regulator activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular Weight:
50618.91 Da