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Details

Stereochemistry ACHIRAL
Molecular Formula C10H17N.ClH
Molecular Weight 187.7099
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMANTADINE HYDROCHLORIDE

SMILES

C1C2CC3CC1CC(C2)(C3)N.Cl

InChI

InChIKey=WOLHOYHSEKDWQH-UHFFFAOYSA-N
InChI=1S/C10H17N.ClH/c11-10-4-7-1-8(5-10)3-9(2-7)6-10;/h7-9H,1-6,11H2;1H

HIDE SMILES / InChI
Amantadine hydrochloride has pharmacological actions as both an anti-Parkinson and an antiviral drug. The mechanism by which amantadine exerts its antiviral activity is not clearly understood. It appears to mainly prevent the release of infectious viral nucleic acid into the host cell by interfering with the function of the transmembrane domain of the viral M2 protein. In certain cases, amantadine is also known to prevent virus assembly during virus replication. It does not appear to interfere with the immunogenicity of inactivated influenza A virus vaccine. The mechanism of action of amantadine in the treatment of Parkinson's disease and drug-induced extrapyramidal reactions is not known. Data from earlier animal studies suggest that amantadine hydrochloride may have direct and indirect effects on dopamine neurons. More recent studies have demonstrated that amantadine is a weak, non-competitive NMDA receptor antagonist (K1 = 10µM). Although amantadine has not been shown to possess direct anticholinergic activity in animal studies, clinically, it exhibits anticholinergic-like side effects such as dry mouth, urinary retention, and constipation. Amantadine was approved by the FDA in 1966 as a prophylactic agent against Asian influenza, and eventually received approval for the treatment of influenza virus A in adults. In 1969, it was also discovered by accident to help reduce symptoms of Parkinson's disease, drug-induced extrapyramidal syndromes, and akathisia.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
MANTADINE HYDROCHLORIDE

Approved Use

Amantadine Hydrochloride Capsules, USP are indicated for the prophylaxis and treatment of signs and symptoms of infection caused by various strains of influenza A virus. Amantadine Hydrochloride Capsules, USP are also indicated in the treatment of parkinsonism and drug-induced extrapyramidal reactions.

Launch Date

540518400000
Primary
MANTADINE HYDROCHLORIDE

Approved Use

Amantadine Hydrochloride Capsules, USP are indicated for the prophylaxis and treatment of signs and symptoms of infection caused by various strains of influenza A virus. Amantadine Hydrochloride Capsules, USP are also indicated in the treatment of parkinsonism and drug-induced extrapyramidal reactions.

Launch Date

540518400000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
636.2 ng/mL
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMANTADINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
0.24 μg/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMANTADINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6413.6 ng × h/mL
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMANTADINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
14.7 h
100 mg 2 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AMANTADINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
33%
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMANTADINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
0.8 g single, oral
Overdose
Dose: 0.8 g
Route: oral
Route: single
Dose: 0.8 g
Sources:
healthy, 2
Health Status: healthy
Age Group: 2
Sex: M
Sources:
Disc. AE: Status epilepticus, Agitation...
AEs leading to
discontinuation/dose reduction:
Status epilepticus
Agitation
Diaphoresis
Vomiting
Sources:
3000 mg single, oral
Overdose
Dose: 3000 mg
Route: oral
Route: single
Dose: 3000 mg
Sources:
unhealthy, 23
Health Status: unhealthy
Age Group: 23
Sex: M
Sources:
Disc. AE: CNS toxicity...
AEs leading to
discontinuation/dose reduction:
CNS toxicity (grade 5)
Sources:
10 g single, oral
Overdose
Dose: 10 g
Route: oral
Route: single
Dose: 10 g
Sources:
unhealthy, 47
Health Status: unhealthy
Age Group: 47
Sex: F
Sources:
Disc. AE: Ventricular tachycardia...
AEs leading to
discontinuation/dose reduction:
Ventricular tachycardia
Sources:
274 mg 1 times / day multiple, oral
Recommended
Dose: 274 mg, 1 times / day
Route: oral
Route: multiple
Dose: 274 mg, 1 times / day
Sources:
unhealthy, 53.3
Health Status: unhealthy
Age Group: 53.3
Sex: M+F
Sources:
Disc. AE: Serotonin syndrome, Dry mouth...
AEs leading to
discontinuation/dose reduction:
Serotonin syndrome (serious, 3.7%)
Dry mouth (3.7%)
Sources:
274 mg 1 times / day multiple, oral
Recommended
Dose: 274 mg, 1 times / day
Route: oral
Route: multiple
Dose: 274 mg, 1 times / day
Sources:
unhealthy, 63.9
Health Status: unhealthy
Age Group: 63.9
Sex: M+F
Sources:
DLT: Visual hallucinations...
Disc. AE: Visual hallucinations, Peripheral edema...
Dose limiting toxicities:
Visual hallucinations (4.8%)
AEs leading to
discontinuation/dose reduction:
Visual hallucinations (7.9%)
Peripheral edema (4.8%)
Dry mouth (4.8%)
Sources:
420 mg 1 times / day multiple, oral
Highest studied dose
Dose: 420 mg, 1 times / day
Route: oral
Route: multiple
Dose: 420 mg, 1 times / day
Sources:
unhealthy, 66.4
Health Status: unhealthy
Age Group: 66.4
Sex: M+F
Sources:
Disc. AE: Hallucinations, Balance disorder...
AEs leading to
discontinuation/dose reduction:
Hallucinations (15%)
Balance disorder (5%)
Confusional state (5%)
Dry mouth (5%)
Subdural hematoma (5%)
Constipation (5%)
Sources:
100 mg 3 times / day steady, oral
Dose: 100 mg, 3 times / day
Route: oral
Route: steady
Dose: 100 mg, 3 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Other AEs: Dry mouth...
Other AEs:
Dry mouth (below serious, 4 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Agitation Disc. AE
0.8 g single, oral
Overdose
Dose: 0.8 g
Route: oral
Route: single
Dose: 0.8 g
Sources:
healthy, 2
Health Status: healthy
Age Group: 2
Sex: M
Sources:
Diaphoresis Disc. AE
0.8 g single, oral
Overdose
Dose: 0.8 g
Route: oral
Route: single
Dose: 0.8 g
Sources:
healthy, 2
Health Status: healthy
Age Group: 2
Sex: M
Sources:
Status epilepticus Disc. AE
0.8 g single, oral
Overdose
Dose: 0.8 g
Route: oral
Route: single
Dose: 0.8 g
Sources:
healthy, 2
Health Status: healthy
Age Group: 2
Sex: M
Sources:
Vomiting Disc. AE
0.8 g single, oral
Overdose
Dose: 0.8 g
Route: oral
Route: single
Dose: 0.8 g
Sources:
healthy, 2
Health Status: healthy
Age Group: 2
Sex: M
Sources:
CNS toxicity grade 5
Disc. AE
3000 mg single, oral
Overdose
Dose: 3000 mg
Route: oral
Route: single
Dose: 3000 mg
Sources:
unhealthy, 23
Health Status: unhealthy
Age Group: 23
Sex: M
Sources:
Ventricular tachycardia Disc. AE
10 g single, oral
Overdose
Dose: 10 g
Route: oral
Route: single
Dose: 10 g
Sources:
unhealthy, 47
Health Status: unhealthy
Age Group: 47
Sex: F
Sources:
Dry mouth 3.7%
Disc. AE
274 mg 1 times / day multiple, oral
Recommended
Dose: 274 mg, 1 times / day
Route: oral
Route: multiple
Dose: 274 mg, 1 times / day
Sources:
unhealthy, 53.3
Health Status: unhealthy
Age Group: 53.3
Sex: M+F
Sources:
Serotonin syndrome serious, 3.7%
Disc. AE
274 mg 1 times / day multiple, oral
Recommended
Dose: 274 mg, 1 times / day
Route: oral
Route: multiple
Dose: 274 mg, 1 times / day
Sources:
unhealthy, 53.3
Health Status: unhealthy
Age Group: 53.3
Sex: M+F
Sources:
Visual hallucinations 4.8%
DLT
274 mg 1 times / day multiple, oral
Recommended
Dose: 274 mg, 1 times / day
Route: oral
Route: multiple
Dose: 274 mg, 1 times / day
Sources:
unhealthy, 63.9
Health Status: unhealthy
Age Group: 63.9
Sex: M+F
Sources:
Dry mouth 4.8%
Disc. AE
274 mg 1 times / day multiple, oral
Recommended
Dose: 274 mg, 1 times / day
Route: oral
Route: multiple
Dose: 274 mg, 1 times / day
Sources:
unhealthy, 63.9
Health Status: unhealthy
Age Group: 63.9
Sex: M+F
Sources:
Peripheral edema 4.8%
Disc. AE
274 mg 1 times / day multiple, oral
Recommended
Dose: 274 mg, 1 times / day
Route: oral
Route: multiple
Dose: 274 mg, 1 times / day
Sources:
unhealthy, 63.9
Health Status: unhealthy
Age Group: 63.9
Sex: M+F
Sources:
Visual hallucinations 7.9%
Disc. AE
274 mg 1 times / day multiple, oral
Recommended
Dose: 274 mg, 1 times / day
Route: oral
Route: multiple
Dose: 274 mg, 1 times / day
Sources:
unhealthy, 63.9
Health Status: unhealthy
Age Group: 63.9
Sex: M+F
Sources:
Hallucinations 15%
Disc. AE
420 mg 1 times / day multiple, oral
Highest studied dose
Dose: 420 mg, 1 times / day
Route: oral
Route: multiple
Dose: 420 mg, 1 times / day
Sources:
unhealthy, 66.4
Health Status: unhealthy
Age Group: 66.4
Sex: M+F
Sources:
Balance disorder 5%
Disc. AE
420 mg 1 times / day multiple, oral
Highest studied dose
Dose: 420 mg, 1 times / day
Route: oral
Route: multiple
Dose: 420 mg, 1 times / day
Sources:
unhealthy, 66.4
Health Status: unhealthy
Age Group: 66.4
Sex: M+F
Sources:
Confusional state 5%
Disc. AE
420 mg 1 times / day multiple, oral
Highest studied dose
Dose: 420 mg, 1 times / day
Route: oral
Route: multiple
Dose: 420 mg, 1 times / day
Sources:
unhealthy, 66.4
Health Status: unhealthy
Age Group: 66.4
Sex: M+F
Sources:
Constipation 5%
Disc. AE
420 mg 1 times / day multiple, oral
Highest studied dose
Dose: 420 mg, 1 times / day
Route: oral
Route: multiple
Dose: 420 mg, 1 times / day
Sources:
unhealthy, 66.4
Health Status: unhealthy
Age Group: 66.4
Sex: M+F
Sources:
Dry mouth 5%
Disc. AE
420 mg 1 times / day multiple, oral
Highest studied dose
Dose: 420 mg, 1 times / day
Route: oral
Route: multiple
Dose: 420 mg, 1 times / day
Sources:
unhealthy, 66.4
Health Status: unhealthy
Age Group: 66.4
Sex: M+F
Sources:
Subdural hematoma 5%
Disc. AE
420 mg 1 times / day multiple, oral
Highest studied dose
Dose: 420 mg, 1 times / day
Route: oral
Route: multiple
Dose: 420 mg, 1 times / day
Sources:
unhealthy, 66.4
Health Status: unhealthy
Age Group: 66.4
Sex: M+F
Sources:
Dry mouth below serious, 4 patients
100 mg 3 times / day steady, oral
Dose: 100 mg, 3 times / day
Route: oral
Route: steady
Dose: 100 mg, 3 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
unlikely
yes [Ki 111.8 uM]
yes [Ki 1167 uM]
yes [Ki 236 uM]
yes [Ki 284 uM]
yes [Ki >1000 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
Blockade of the central effects of d-amphetamine by amantadine. II.
1975 May
Visual hallucinations and delirium during treatment with amantadine (Symmetrel).
1975 May
Differential inhibitory effects of sulfated polysaccharides and polymers on the replication of various myxoviruses and retroviruses, depending on the composition of the target amino acid sequences of the viral envelope glycoproteins.
1991 Dec
Neurotoxicity of chlorpromazine and modulation by amantadine as a function of mouse strain.
1991 Fall
Amantadine as N-methyl-D-aspartic acid receptor antagonist: new possibilities for therapeutic applications?
1992
A trigger for Tourette's syndrome.
1992 Mar
Successful treatment of levodopa-induced neuroleptic malignant syndrome (NMS) and disseminated intravascular coagulation (DIC) in a patient with Parkinson's disease.
1992 Nov
Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.
1992 Sep
Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia.
1992 Sep
Amantadine-induced multiple spike waves on an electroencephalogram of a schizophrenic patient.
2000 Jan
Comparison of colorimetric, fluorometric, and visual methods for determining anti-influenza (H1N1 and H3N2) virus activities and toxicities of compounds.
2002 Oct
Amantadine in Huntington's disease: open-label video-blinded study.
2002 Sep
Huntington's disease: a randomized, controlled trial using the NMDA-antagonist amantadine.
2002 Sep 10
NMDA receptor antagonists to characterize rat renal organic cation transporter function.
2002 Sep 27
Synthesis and antioxidant activity evaluation of novel antiparkinsonian agents, aminoadamantane derivatives of nitroxyl free radical.
2003 Aug 5
Heterocyclic rimantadine analogues with antiviral activity.
2003 Dec 1
An artist's view of drug-induced hallucinosis.
2003 Jul
Synthesis of 1-boraadamantaneamine derivatives with selective astrocyte vs C6 glioma antiproliferative activity. A novel class of anti-hepatitis C agents with potential to bind CD81.
2003 Jul 3
Mirtazapine in L-dopa-induced dyskinesias.
2003 Jul-Aug
Noncompetitive antagonist binding sites in the torpedo nicotinic acetylcholine receptor ion channel. Structure-activity relationship studies using adamantane derivatives.
2003 Jun 24
Risperidone treatment of motor restlessness following anoxic brain injury.
2003 Mar
Spiro[pyrrolidine-2,2'-adamantanes]: synthesis, anti-influenza virus activity and conformational properties.
2003 May 19
Livedo reticularis induced by amantadine.
2003 Sep
Peginterferon alpha-2b plus ribavirin with or without amantadine [correction of amantidine] for the treatment of non-responders to standard interferon and ribavirin.
2004 Aug
Effects of perioperative oral amantadine on postoperative pain and morphine consumption in patients after radical prostatectomy: results of a preliminary study.
2004 Jan
Motor-learning impairment by amantadine in healthy volunteers.
2004 Jan
Liquid chromatographic determination of 1-adamantanamine and 2-adamantanamine in human plasma after pre-column derivatization with o-phthalaldehyde and 1-thio-beta-D-glucose.
2004 Jan 25
Treatment of interferon non-responsive chronic hepatitis C with triple therapy with interferon, ribavirin, and amantidine can be encouraging.
2004 Mar
[Comparative study of neurophysiological effects of adamantane derivatives in the experimental parkinsonism model].
2004 Mar-Apr
The potential anti-hBV effect of amantadine in combination with ursodeoxycholic acid and biphenyl dimethyl dicarboxylate in hepG2 2.2.15 cells.
2005 Apr
Improved neurological function after Amantadine treatment in two patients with brain injury.
2005 Apr
Site-isolated porphyrin catalysts in imprinted polymers.
2005 Aug 19
High effectiveness of platinum(IV) complex with adamantylamine in overcoming resistance to cisplatin and suppressing proliferation of ovarian cancer cells in vitro.
2005 Feb 1
Preclinical anti-tumor activity of a new oral platinum(IV) drug LA-12.
2005 Jul
Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia.
2005 Jul
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Amantadine reduces the duration of levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study.
2005 Nov
Low-dose levodopa therapy in Japanese patients with Parkinson's disease: a retrospective study.
2005 Sep
Determination of serum amantadine by liquid chromatography-tandem mass spectrometry.
2005 Sep
Glutamate receptors in neuroinflammatory demyelinating disease.
2006
Comparative anti-tumor efficacy of two orally administered platinum(IV) drugs in nude mice bearing human tumor xenografts.
2006 Feb
A novel soluble mimic of the glycolipid, globotriaosyl ceramide inhibits HIV infection.
2006 Feb 14
[Cytosine demethylation in the tyrosine hydroxylase gene promoter in the hypothalamus cells of the rat brain under the action of an aminoadamantane derivative Ladasten].
2006 Jul
The pharmacology of aminoadamantane nitrates.
2006 Jul
Platinum(IV) complex with adamantylamine overcomes intrinsic resistance to cisplatin in ovarian cancer cells.
2006 Jul
Simultaneous liquid chromatographic assay of amantadine and its four related compounds in phosphate-buffered saline using 4-fluoro-7-nitro-2,1,3-benzoxadiazole as a fluorescent derivatization reagent.
2006 May
Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson's disease.
2006 Nov
Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line.
2006 Sep 15
Modulation of L-DOPA-induced abnormal involuntary movements by clinically tested compounds: further validation of the rat dyskinesia model.
2007 Apr 16
19F NMR detection of the complex between amantadine and the receptor portion of the influenza A M2 ion channel in DPC micelles.
2007 Jul 15
Patents

Sample Use Guides

Uncomplicated Influenza A Virus Illness:
Route of Administration: Oral
Amantadine markedly inhibited the proliferation of HepG2 and SMMC‑7721 cells in a dose‑ and time‑dependent manner and arrested the cell cycle at the G0/G1 phase
Name Type Language
AMANTADINE HYDROCHLORIDE
EP   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
MANTADIX
Brand Name English
AMANTADINE HYDROCHLORIDE [MI]
Common Name English
ADAMANTANAMINE HYDROCHLORIDE
Systematic Name English
SYMMETREL
Brand Name English
AMANTADINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
AMANTADINE HYDROCHLORIDE [USP]
Common Name English
AMANTADINE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
AMANTADINE HYDROCHLORIDE [USP-RS]
Common Name English
AMANTADINE HYDROCHLORIDE [VANDF]
Common Name English
OSMOLEX
Brand Name English
AMANTADINE HYDROCHLORIDE [MART.]
Common Name English
SYMADINE
Brand Name English
AMANTADINE HCL
Common Name English
NSC-83653
Code English
AMANTADINE HYDROCHLORIDE [JAN]
Common Name English
TRICYCLO(3.3.1.1(SUP 3,7))DECAN-1-AMINE, HYDROCHLORIDE
Common Name English
AMANTADINE HYDROCHLORIDE [USAN]
Common Name English
EXP-105-1
Code English
AMANTADINE HYDROCHLORIDE [WHO-DD]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 413213
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
NCI_THESAURUS C93038
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
NCI_THESAURUS C281
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
FDA ORPHAN DRUG 257608
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
Code System Code Type Description
PUBCHEM
64150
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
PRIMARY
DRUG BANK
DBSALT000203
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
PRIMARY
USP_CATALOG
1018505
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
PRIMARY USP-RS
ChEMBL
CHEMBL660
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
PRIMARY
RXCUI
282415
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
PRIMARY RxNorm
EVMPD
SUB00422MIG
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
PRIMARY
FDA UNII
M6Q1EO9TD0
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
PRIMARY
CAS
665-66-7
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
PRIMARY
MERCK INDEX
M1638
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
PRIMARY Merck Index
ECHA (EC/EINECS)
211-560-2
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
PRIMARY
NCI_THESAURUS
C28818
Created by admin on Fri Jun 25 21:15:10 UTC 2021 , Edited by admin on Fri Jun 25 21:15:10 UTC 2021
PRIMARY