Identification

Name
Amantadine
Accession Number
DB00915  (APRD00787)
Type
Small Molecule
Groups
Approved
Description

An 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]

Structure
Thumb
Synonyms
  • 1-adamantanamine
  • 1-adamantylamine
  • 1-aminoadamantane
  • Amantadina
  • Amantadine
  • Amantadinum
  • Amantidine
  • Aminoadamantane
  • 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
Product Ingredients
IngredientUNIICASInChI Key
Amantadine hydrochlorideM6Q1EO9TD0665-66-7WOLHOYHSEKDWQH-UHFFFAOYSA-N
Amantadine sulfate9921T5P01931377-23-8MYWTWSQFJLXGGQ-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Amantadine HydrochlorideSolution100 mg/10mLOralPharmaceutical Associates, Inc.2006-10-072007-05-31Us
Amantadine HydrochlorideSyrup50 mg/5mLOralVintage Pharmaceuticals, LLC2007-05-312007-05-31Us
EndantadineCapsule100 mgOralBristol Myers Squibb1993-12-312008-04-25Canada
Endantadine Cap 100mgCapsule100 mgOralDupont Merck Pharma Inc.1993-12-311999-07-20Canada
GocovriCapsule, coated pellets137 mg/1OralAdamas Pharma, Llc2017-08-24Not applicableUs
GocovriCapsule, coated pellets68.5 mg/1OralAdamas Pharma, Llc2017-08-24Not applicableUs
Osmolex ERTablet, extended release193 mg/1OralVertical Pharmaceuticals, LLC2018-06-01Not applicableUs
Osmolex ERTablet, extended release129 mg/1OralVertical Pharmaceuticals, LLC2018-06-01Not applicableUs
Osmolex ERTablet, extended release258 mg/1OralVertical Pharmaceuticals, LLC2018-06-01Not applicableUs
SymmetrelTablet100 mg/1OralEndo Pharmaceuticals1980-11-032007-04-30Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AmantadineCapsule100 mg/1OralAlembic Pharmaceuticals Inc.2017-06-22Not applicableUs
AmantadineCapsule100 mg/1OralAlembic Pharmaceuticals Limited2017-06-22Not applicableUs
Amantadine HClCapsule100 mg/1Oralbryant ranch prepack2008-11-01Not applicableUs
Amantadine HClCapsule, liquid filled100 mg/1OralAv Kare, Inc.2013-08-07Not applicableUs
Amantadine HClCapsule100 mg/1OralRebel Distributors2008-11-01Not applicableUs
Amantadine HClCapsule, liquid filled100 mg/1Oralbryant ranch prepack2016-08-15Not applicableUs
Amantadine HClCapsule, liquid filled100 mg/1OralBionpharma Inc.2016-08-15Not applicableUs
Amantadine HClCapsule, liquid filled100 mg/1OralAv Pak2014-03-28Not applicableUs
Amantadine HClCapsule, liquid filled100 mg/1OralPreferreed Pharmaceuticals Inc.2013-12-20Not applicableUs
Amantadine HClCapsule100 mg/1OralPreferreed Pharmaceuticals Inc.2008-11-012012-09-30Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Gapeam BudibacAmantadine hydrochloride (1 g/1g) + Baclofen (1 g/1g) + Bupivacaine hydrochloride (1 g/1g) + Cyclobenzaprine Hydrochloride (1 g/1g) + Diclofenac sodium (1 g/1g) + Gabapentin (1 g/1g) + Pentoxifylline (1 g/1g)KitTopicalAlvix Laboratories2014-12-052018-03-08Us
Innoprax-5Amantadine hydrochloride (8 g/8g) + Baclofen (3 g/3g) + Diclofenac sodium (3 g/3g) + Gabapentin (6 g/6g) + Lidocaine hydrochloride (5 g/5g)KitAccumix Pharmaceuticals2014-12-152015-07-17Us
International/Other Brands
PK-Merz / Symadine / Symmetrel (Endo Pharmaceuticals)
Categories
UNII
BF4C9Z1J53
CAS number
768-94-5
Weight
Average: 151.2487
Monoisotopic: 151.136099549
Chemical Formula
C10H17N
InChI Key
DKNWSYNQZKUICI-UHFFFAOYSA-N
InChI
InChI=1S/C10H17N/c11-10-4-7-1-8(5-10)3-9(2-7)6-10/h7-9H,1-6,11H2
IUPAC Name
adamantan-1-amine
SMILES
NC12CC3CC(CC(C3)C1)C2

Pharmacology

Indication

For 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.

Associated Conditions
Pharmacodynamics

Amantadine is an antiviral drug which also acts as an antiparkinson agent, for which it is usually combined with L-DOPA when L-DOPA responses decline (probably due to tolerance). It is a derivate of adamantane, like a similar drug rimantadine. The mechanism of action of amantadine in the treatment of Parkinson's disease and drug-induced extrapyramidal reactions is not known. It has been shown to cause an increase in dopamine release in the animal brain, and does not possess anticholinergic activity.

Mechanism of action

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. 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.

TargetActionsOrganism
AMatrix protein 2
inhibitor
Influenza A virus (strain A/Ann Arbor/6/1960 H2N2)
AGlutamate receptor ionotropic, NMDA 3A
antagonist
Human
UNeuronal acetylcholine receptor subunit alpha-7
antagonist
Human
AD(2) dopamine receptor
agonist
Human
UNeuronal acetylcholine receptor subunit alpha-4
antagonist
Human
UNeuronal acetylcholine receptor subunit alpha-3
antagonist
Human
Absorption

Amantadine is well absorbed orally from the gastrointestinal tract.

Volume of distribution
  • 3 to 8 L/kg [healthy subjects]
Protein binding

Approximately 67% bound to plasma proteins over a concentration range of 0.1 to 2.0 µg/mL.

Metabolism

No appreciable metabolism, although negligible amounts of an acetyl metabolite have been identified.

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.

Clearance
  • 0.2 - 0.3 L/hr/kg
  • 0.10 +/- 0.04 L/hr/kg [healthy, elderly male]
Toxicity

Deaths 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.

Affected organisms
  • Humans and other mammals
  • Various viruses
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Amantadine can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Amantadine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Amantadine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Amantadine is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Amantadine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of serotonin syndrome can be increased when Amantadine is combined with 5-methoxy-N,N-dimethyltryptamine.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of serotonin syndrome can be increased when Amantadine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AbacavirAmantadine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbexinostatThe risk or severity of QTc prolongation can be increased when Amantadine is combined with Abexinostat.
AcarboseAcarbose may decrease the excretion rate of Amantadine which could result in a higher serum level.
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.

References

Synthesis Reference

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

General References
Not Available
External Links
Human Metabolome Database
HMDB0015051
KEGG Compound
C06818
PubChem Compound
2130
PubChem Substance
46507081
ChemSpider
2045
BindingDB
50033369
ChEBI
2618
ChEMBL
CHEMBL660
Therapeutic Targets Database
DAP000781
PharmGKB
PA448360
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Amantadine
ATC Codes
N04BB01 — Amantadine
AHFS Codes
  • 08:18.04 — Adamantanes
  • 28:36.04 — Adamantanes
FDA label
Download (197 KB)
MSDS
Download (73.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedDiagnosticCocaine-Related Disorders / Substance-Related Disorders1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentMood Disorders With Psychotic Features / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder1
1, 2CompletedTreatmentFlu caused by Influenza1
1, 2Unknown StatusEducational/Counseling/TrainingHyperalgesia / Pain NOS / Prostate Cancer1
2CompletedTreatmentAnoxia / Comatose / Heart Arrest1
2CompletedTreatmentChorea / Huntington's Disease (HD)1
2CompletedTreatmentCocaine-Related Disorders2
2CompletedTreatmentDisseminated Sclerosis / Walking Impairment1
2CompletedTreatmentFlu caused by Influenza2
2CompletedTreatmentType 2 Diabetes Mellitus1
2RecruitingDiagnosticMalignancies1
2RecruitingPreventionIntubation, Intratracheal1
2RecruitingTreatmentParkinson's Disease (PD)1
2TerminatedTreatmentInfluenza A Infection1
2TerminatedTreatmentParkinson's Disease (PD) / Perioperative Care1
2Unknown StatusTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)1
2, 3CompletedTreatmentDyskinesias / Levodopa Induced Dyskinesia (LID) / Parkinson's Disease (PD)1
2, 3CompletedTreatmentTraumatic Brain Injury (TBI)1
3Active Not RecruitingTreatmentDyskinesias / Levodopa Induced Dyskinesia (LID) / Parkinson's Disease (PD)1
3CompletedPreventionSchizoaffective Disorders / Schizophrenic Disorders1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Hepatitis C Virus (HCV) Infection1
3CompletedTreatmentDyskinesias / Levodopa Induced Dyskinesia (LID) / Parkinson's Disease (PD)1
3CompletedTreatmentDyskinesias / Levodopa-Induced Dyskinesia (LID) / Parkinson's Disease (PD)1
3RecruitingTreatmentDisseminated Sclerosis / Walking Impairment2
3RecruitingTreatmentFatigue in Multiple Sclerosis1
3TerminatedTreatmentChronic Hepatitis C Virus (HCV) Infection1
3TerminatedTreatmentLevodopa Induced Dyskinesia (LID) / Parkinson's Disease (PD)1
3TerminatedTreatmentLevodopa Induced Dyskinesias (LID) / Parkinson's Disease (PD)1
3TerminatedTreatmentParkinson's Disease (PD)1
3Unknown StatusTreatmentSchizophrenic Disorders1
4Active Not RecruitingTreatmentIntensive Care Units1
4CompletedNot AvailableParkinson's Disease (PD)1
4CompletedTreatmentAtaxia / Chorea / Dystonias / Parkinsonism / Tiredness1
4CompletedTreatmentParkinson's Disease (PD)1
4RecruitingTreatmentTraumatic Brain Injury (TBI)1
4TerminatedTreatmentDementias1
4TerminatedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
4Unknown StatusTreatmentDelirium / Posttraumatic Confusional State / Traumatic Brain Injury (TBI)1
Not AvailableActive Not RecruitingTreatmentTraumatic Brain Injury (TBI)1
Not AvailableCompletedDiagnosticHealthy Metabolism1
Not AvailableCompletedTreatmentAggressive Behavior / Brain Injury1
Not AvailableCompletedTreatmentAggressive Behavior / Irritability / Traumatic Brain Injury (TBI)1
Not AvailableNot Yet RecruitingNot AvailableAcquired Brain Injury / Comatose / Minimally Conscious State / Persistent Vegetative State / Traumatic Brain Injury (TBI)1
Not AvailableNot Yet RecruitingTreatmentPostoperative Cognitive Dysfunction1
Not AvailableRecruitingNot AvailableAtypical Parkinson Disease / Corticobasal Degeneration / Gait, Frontal / Multiple System Atrophy (MSA) / Parkinson's Disease (PD) / Parkinsonian Disorders / Progressive Supranuclear Palsy (PSP)1
Not AvailableTerminatedBasic ScienceTraumatic Brain Injury (TBI)1
Not AvailableTerminatedTreatmentParkinson's Disease (PD)1
Not AvailableUnknown StatusTreatmentParkinson's Disease (PD)1

Pharmacoeconomics

Manufacturers
  • Actavis totowa llc
  • Banner pharmacaps inc
  • Sandoz inc
  • Usl pharma inc
  • Watson laboratories inc
  • Solvay pharmaceuticals
  • Endo pharmaceuticals inc
  • Actavis mid atlantic llc
  • Carolina medical products co
  • Hi tech pharmacal co inc
  • Mikart inc
  • Pharmaceutical assoc inc div beach products
  • Silarx pharmaceuticals inc
  • Teva pharmaceuticals usa
  • Vintage pharmaceuticals llc
  • Wockhardt eu operations (swiss) ag
Packagers
  • Anip Acquisition Co.
  • A-S Medication Solutions LLC
  • Banner Pharmacaps Inc.
  • Bristol-Myers Squibb Co.
  • Carolina Medical Products Co.
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Endo Pharmaceuticals Inc.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Hi Tech Pharmacal Co. Inc.
  • Lake Erie Medical and Surgical Supply
  • Lannett Co. Inc.
  • Major Pharmaceuticals
  • Mikart Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patient First Corp.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Association
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Qualitest
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Sandoz
  • Southwood Pharmaceuticals
  • Spectrum Pharmaceuticals
  • Tya Pharmaceuticals
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Upsher Smith Laboratories
  • USL Pharma Inc.
  • Vangard Labs Inc.
  • Vintage Pharmaceuticals Inc.
  • Wockhardt Ltd.
Dosage forms
FormRouteStrength
Capsule, liquid filledOral100 mg/1
CapsuleOral100 mg/1
Capsule, gelatin coatedOral100 mg/1
SolutionOral100 mg/10mL
SolutionOral50 mg/5mL
Tablet, film coatedOral100 mg/1
KitTopical
Capsule, coated pelletsOral137 mg/1
Capsule, coated pelletsOral68.5 mg/1
Kit
Tablet, extended releaseOral129 mg/1
Tablet, extended releaseOral193 mg/1
Tablet, extended releaseOral258 mg/1
SyrupOral50 mg/5mL
TabletOral100 mg/1
CapsuleOral100 mg
SyrupOral10 mg
Prices
Unit descriptionCostUnit
Symmetrel 50 mg/5ml Syrup 480ml Bottle151.46USD bottle
Amantadine hcl powder6.7USD g
Symmetrel 100 mg tablet1.45USD tablet
Amantadine HCl 100 mg tablet1.37USD tablet
Amantadine 100 mg tablet1.32USD tablet
Amantadine HCl 100 mg capsule0.78USD capsule
Mylan-Amantadine 100 mg Capsule0.54USD capsule
Pms-Amantadine Hydrochloride 100 mg Capsule0.54USD capsule
Amantadine HCl 50 mg/5ml Syrup0.16USD ml
Pms-Amantadine Hydrochloride 10 mg/ml Syrup0.09USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
USRE39069No1998-05-292018-05-29Us
US8895616No2005-11-232025-11-23Us
US8895617No2005-11-232025-11-23Us
US8741343No2010-12-022030-12-02Us
US8895615No2005-11-232025-11-23Us
US8796337No2005-11-232025-11-23Us
US8389578No2008-01-222028-01-22Us
US8895618No2005-11-232025-11-23Us
US8895614No2005-11-232025-11-23Us
US8889740No2005-11-232025-11-23Us
US9867792No2010-12-022030-12-02Us
US9867793No2010-12-022030-12-02Us
US9867791No2010-12-022030-12-02Us
US9877933No2010-12-022030-12-02Us
US8574626No2005-11-282025-11-28Us
US8252331No2010-03-132030-03-13Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)180-192Haaf, W.; U.S. Patent 3,152,180; October 6, 1964; assigned to Studiengesellschaft Kohle mbH, Germany.
water solubility6290 mg/L (freely soluble)Not Available
logP2.44HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0846 mg/mLALOGPS
logP2.53ALOGPS
logP1.47ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)10.71ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area26.02 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity45.54 m3·mol-1ChemAxon
Polarizability17.92 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9903
Blood Brain Barrier+0.9769
Caco-2 permeable+0.6248
P-glycoprotein substrateNon-substrate0.7275
P-glycoprotein inhibitor INon-inhibitor0.9277
P-glycoprotein inhibitor IINon-inhibitor0.8549
Renal organic cation transporterNon-inhibitor0.7474
CYP450 2C9 substrateNon-substrate0.8306
CYP450 2D6 substrateNon-substrate0.7092
CYP450 3A4 substrateNon-substrate0.6561
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5886
Ames testNon AMES toxic0.7836
CarcinogenicityNon-carcinogens0.7647
BiodegradationNot ready biodegradable0.9456
Rat acute toxicity2.2564 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9779
hERG inhibition (predictor II)Non-inhibitor0.8695
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.71 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-014i-1910000000-c4908efe87e5cdf2ba74
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-014i-1910000000-8b7366cc494bf757bb81
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-01b9-6910000000-e6fd5b29f51169a772e5
Mass Spectrum (Electron Ionization)MSsplash10-0006-9100000000-44ff981fd5fa6c48df97
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0f79-0900000000-b3511c6e5de6fce544c6
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0f79-0900000000-ca740a06e33d4850b211
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-000i-0900000000-f1084780a2940c5afd1b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-000i-0900000000-a083f7fdcbb679c2996a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-000i-2900000000-496b35f0cfba5aa930ed
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-000i-7900000000-e37809d5efe023b0382d
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-0900000000-1a8aac6647f0187ebdf9
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000i-0900000000-88a4152a7398da21333c
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000i-1900000000-76e73b05fc9ac0bdc170
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-002u-9600000000-048cdcfd022184f574b6
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-004l-9000000000-8bc5ffed5487b0edffaf
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0900000000-4aa7b04aaac47d693e8d
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udr-0900000000-815d4b207b027466d755
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-7ce8af9197b4d35ecffd
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-278de51184b1c34ed88f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-1a9620db53d99baf9c05
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-1a9620db53d99baf9c05
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0f79-1900000000-f49f767b2078c543faad
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as monoalkylamines. These are organic compounds containing an primary aliphatic amine group.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Monoalkylamines
Alternative Parents
Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Organopnictogen compound / Hydrocarbon derivative / Primary aliphatic amine / Aliphatic homopolycyclic compound
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
adamantanes, primary aliphatic amine (CHEBI:2618)

Targets

Kind
Protein
Organism
Influenza A virus (strain A/Ann Arbor/6/1960 H2N2)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ion channel activity
Specific Function
Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytos...
Gene Name
M
Uniprot ID
P21430
Uniprot Name
Matrix protein 2
Molecular Weight
11165.62 Da
References
  1. Wang C, Takeuchi K, Pinto LH, Lamb RA: Ion channel activity of influenza A virus M2 protein: characterization of the amantadine block. J Virol. 1993 Sep;67(9):5585-94. [PubMed:7688826]
  2. Jing X, Ma C, Ohigashi Y, Oliveira FA, Jardetzky TS, Pinto LH, Lamb RA: Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10967-72. doi: 10.1073/pnas.0804958105. Epub 2008 Jul 31. [PubMed:18669647]
  3. Wang J, Cady SD, Balannik V, Pinto LH, DeGrado WF, Hong M: Discovery of spiro-piperidine inhibitors and their modulation of the dynamics of the M2 proton channel from influenza A virus. J Am Chem Soc. 2009 Jun 17;131(23):8066-76. doi: 10.1021/ja900063s. [PubMed:19469531]
  4. Beigel J, Bray M: Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102. doi: 10.1016/j.antiviral.2008.01.003. Epub 2008 Feb 4. [PubMed:18328578]
  5. Lear JD: Proton conduction through the M2 protein of the influenza A virus; a quantitative, mechanistic analysis of experimental data. FEBS Lett. 2003 Sep 18;552(1):17-22. [PubMed:12972146]
  6. Salom D, Hill BR, Lear JD, DeGrado WF: pH-dependent tetramerization and amantadine binding of the transmembrane helix of M2 from the influenza A virus. Biochemistry. 2000 Nov 21;39(46):14160-70. [PubMed:11087364]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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 ...
Gene Name
GRIN3A
Uniprot ID
Q8TCU5
Uniprot Name
Glutamate receptor ionotropic, NMDA 3A
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. [PubMed: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 (Vienna). 1999;106(5-6):409-21. [PubMed:10443547]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Toxic substance binding
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The cha...
Gene Name
CHRNA7
Uniprot ID
P36544
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-7
Molecular Weight
56448.925 Da
References
  1. Matsubayashi H, Swanson KL, Albuquerque EX: Amantadine inhibits nicotinic acetylcholine receptor function in hippocampal neurons. J Pharmacol Exp Ther. 1997 May;281(2):834-44. [PubMed:9152392]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Tomitaka S, Hashimoto K, Narita N, Minabe Y, Tamura A: Amantadine induces c-fos in rat striatum: reversal with dopamine D1 and NMDA receptor antagonists. Eur J Pharmacol. 1995 Oct 16;285(2):207-11. [PubMed:8566141]
  2. Ameri A: Effects of the Aconitum alkaloid songorine on synaptic transmission and paired-pulse facilitation of CA1 pyramidal cells in rat hippocampal slices. Br J Pharmacol. 1998 Oct;125(3):461-8. [PubMed:9806328]
  3. 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 (Vienna). 1999;106(5-6):409-21. [PubMed:10443547]
  4. Cousins MS, Carriero DL, Salamone JD: Tremulous jaw movements induced by the acetylcholinesterase inhibitor tacrine: effects of antiparkinsonian drugs. Eur J Pharmacol. 1997 Mar 19;322(2-3):137-45. [PubMed:9098680]
  5. doi:10.1007/s00415-006-3004-8 [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Ligand-gated ion channel activity
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeabl...
Gene Name
CHRNA4
Uniprot ID
P43681
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-4
Molecular Weight
69956.47 Da
References
  1. Matsubayashi H, Swanson KL, Albuquerque EX: Amantadine inhibits nicotinic acetylcholine receptor function in hippocampal neurons. J Pharmacol Exp Ther. 1997 May;281(2):834-44. [PubMed:9152392]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Ligand-gated ion channel activity
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name
CHRNA3
Uniprot ID
P32297
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-3
Molecular Weight
57479.54 Da
References
  1. Matsubayashi H, Swanson KL, Albuquerque EX: Amantadine inhibits nicotinic acetylcholine receptor function in hippocampal neurons. J Pharmacol Exp Ther. 1997 May;281(2):834-44. [PubMed:9152392]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Pyridoxal phosphate binding
Specific Function
Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
Gene Name
DDC
Uniprot ID
P20711
Uniprot Name
Aromatic-L-amino-acid decarboxylase
Molecular Weight
53925.815 Da
References
  1. Li XM, Juorio AV, Qi J, Boulton AA: Amantadine increases aromatic L-amino acid decarboxylase mRNA in PC12 cells. J Neurosci Res. 1998 Aug 15;53(4):490-3. [PubMed:9710269]
  2. Fisher A, Biggs CS, Starr MS: Effects of glutamate antagonists on the activity of aromatic L-amino acid decarboxylase. Amino Acids. 1998;14(1-3):43-9. [PubMed:9871440]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Primary amine oxidase activity
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOB
Uniprot ID
P27338
Uniprot Name
Amine oxidase [flavin-containing] B
Molecular Weight
58762.475 Da
References
  1. Wesemann W, Ekenna O: Effect of 1-aminoadamantanes on the MAO activity in brain, liver, and kidney of the rat. Arzneimittelforschung. 1982;32(10):1241-3. [PubMed:6891223]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. [PubMed:12089365]
  2. 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. [PubMed:9687576]
  3. Goralski KB, Lou G, Prowse MT, Gorboulev V, Volk C, Koepsell H, Sitar DS: The cation transporters rOCT1 and rOCT2 interact with bicarbonate but play only a minor role for amantadine uptake into rat renal proximal tubules. J Pharmacol Exp Ther. 2002 Dec;303(3):959-68. [PubMed:12438515]
  4. Ishiguro N, Saito A, Yokoyama K, Morikawa M, Igarashi T, Tamai I: Transport of the dopamine D2 agonist pramipexole by rat organic cation transporters OCT1 and OCT2 in kidney. Drug Metab Dispos. 2005 Apr;33(4):495-9. Epub 2005 Jan 7. [PubMed:15640376]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. [PubMed:12606755]
  2. Zhang L, Schaner ME, Giacomini KM: Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther. 1998 Jul;286(1):354-61. [PubMed:9655880]
  3. Goralski KB, Lou G, Prowse MT, Gorboulev V, Volk C, Koepsell H, Sitar DS: The cation transporters rOCT1 and rOCT2 interact with bicarbonate but play only a minor role for amantadine uptake into rat renal proximal tubules. J Pharmacol Exp Ther. 2002 Dec;303(3):959-68. [PubMed:12438515]
  4. Ishiguro N, Saito A, Yokoyama K, Morikawa M, Igarashi T, Tamai I: Transport of the dopamine D2 agonist pramipexole by rat organic cation transporters OCT1 and OCT2 in kidney. Drug Metab Dispos. 2005 Apr;33(4):495-9. Epub 2005 Jan 7. [PubMed:15640376]

Drug created on June 13, 2005 07:24 / Updated on November 13, 2018 07:53