AMANTADINE SULFATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	2C10H17N.H2O4S
Molecular Weight	400.5777
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C1C2CC3CC1CC(C2)(C3)N.C1C2CC3CC1CC(C2)(C3)N.OS(=O)(=O)O

InChI

InChIKey=MYWTWSQFJLXGGQ-UHFFFAOYSA-N

InChI=1S/2C10H17N.H2O4S/c2*11-10-4-7-1-8(5-10)3-9(2-7)6-10;1-5(2,3)4/h2*7-9H,1-6,11H2;(H2,1,2,3,4)

HIDE SMILES / InChI

Molecular Formula	H2O4S
Molecular Weight	98.0796
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C10H17N
Molecular Weight	151.2491
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6e6e111-38da-43a2-b6c4-15e69b720495

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.

CNS Activity

Originator

Approval Year

Conditions

Condition	Modality	Targets	Highest Phase	Product
Influenza A virus infection 9 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6e6e111-38da-43a2-b6c4-15e69b720495	Primary		Approved 7998	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
Parkinson's disease 218 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6e6e111-38da-43a2-b6c4-15e69b720495	Primary		Approved 7998	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

Value	Dose	Co-administered	Analyte	Population
636.2 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18074029	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016023s041,018101s016lbl.pdf	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

Value	Dose	Co-administered	Analyte	Population
6413.6 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18074029	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

Value	Dose	Co-administered	Analyte	Population
14.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18074029	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

Value	Dose	Co-administered	Analyte	Population
33% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016023s041,018101s016lbl.pdf	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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1386 inhibitor 1093	substrate 808 inhibitor 1234	substrate 981 inhibitor 1315

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1168 CYP2B6 642 CYP2C19 1136 CYP2C8 712 CYP2E1 692 CYP3A5 63 OCT1 425 OCT2 538 OCT3 132 MATE1 259 MATE2 240	CYP1A2 837 CYP2B6 538 CYP2C19 780 CYP2C8 539 CYP2E1 516 CYP3A5 310 OCT2 276

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1302	inhibitor 2421 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2B6 787	inhibitor 2421 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2C19 1193	inhibitor 2421 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2C8 744	inhibitor 2421 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2C9 1273	inhibitor 2421 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2D6 1349	inhibitor 2421 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2E1 769	inhibitor 2421 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP3A4 1367	inhibitor 2421 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP3A5 91	inhibitor 2421 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
MATE1 260	inhibitor 2421 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 111.8 uM]
MATE2 240	inhibitor 2421 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 1167 uM]
OCT1 436	inhibitor 2421 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 236 uM]
OCT2 539	inhibitor 2421 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 284 uM]
OCT3 132	inhibitor 2421 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki >1000 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 837	substrate 2552 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2B6 538	substrate 2552 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2C19 780	substrate 2552 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2C8 539	substrate 2552 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2C9 808	substrate 2552 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2D6 981	substrate 2552 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2E1 516	substrate 2552 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP3A4 1386	substrate 2552 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP3A5 310	substrate 2552 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
OCT2 276	substrate 2552 Sources: https://pubmed.ncbi.nlm.nih.gov/9687576/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2618	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2618
MolPort	MolPort-001-661-700	https://www.molport.com/shop/molecule-link/MolPort-001-661-700
MolPort	MolPort-020-000-111	https://www.molport.com/shop/molecule-link/MolPort-020-000-111
ZINC	ZINC000000968256	http://zinc15.docking.org/substances/ZINC000000968256

PubMed

Title	Date	PubMed
Visual hallucinations and delirium during treatment with amantadine (Symmetrel).	1975 May	123540
Neurotoxicity of chlorpromazine and modulation by amantadine as a function of mouse strain.	1991 Fall	1745440
Amantadine as N-methyl-D-aspartic acid receptor antagonist: new possibilities for therapeutic applications?	1992	1320514
A trigger for Tourette's syndrome.	1992 Mar	1564044
Successful treatment of levodopa-induced neuroleptic malignant syndrome (NMS) and disseminated intravascular coagulation (DIC) in a patient with Parkinson's disease.	1992 Nov	1295627
Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.	1992 Sep	1416885
Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia.	1992 Sep	1416884
Amantadine-induced multiple spike waves on an electroencephalogram of a schizophrenic patient.	2000 Jan	12611370
The role of glutamatergic transmission in the pathogenesis of levodopa-induced dyskinesias. Potential therapeutic approaches.	2001	12001656
[The use of amantadine sulfate in combined therapy of Parkinson's disease].	2002	12161861
Nitecapone and selegiline as effective adjuncts to L-DOPA in reserpine-induced catatonia in mice.	2002 Jan-Feb	11980384
A screening trial of amantadine as a medication for cocaine dependence.	2002 May 1	12062456
Amantadine in Huntington's disease: open-label video-blinded study.	2002 Sep	12548355
Huntington's disease: a randomized, controlled trial using the NMDA-antagonist amantadine.	2002 Sep 10	12221159
NMDA receptor antagonists to characterize rat renal organic cation transporter function.	2002 Sep 27	12323380
[Cortico-basal degeneration: the rare form of tau protein disease].	2003	15098333
Synthesis and antioxidant activity evaluation of novel antiparkinsonian agents, aminoadamantane derivatives of nitroxyl free radical.	2003 Aug 5	12878145
Heterocyclic rimantadine analogues with antiviral activity.	2003 Dec 1	14642592
An artist's view of drug-induced hallucinosis.	2003 Jul	12815666
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	12825926
Mirtazapine in L-dopa-induced dyskinesias.	2003 Jul-Aug	12897636
Noncompetitive antagonist binding sites in the torpedo nicotinic acetylcholine receptor ion channel. Structure-activity relationship studies using adamantane derivatives.	2003 Jun 24	12809491
Risperidone treatment of motor restlessness following anoxic brain injury.	2003 Mar	12623500
Spiro[pyrrolidine-2,2'-adamantanes]: synthesis, anti-influenza virus activity and conformational properties.	2003 May 19	12729645
Livedo reticularis induced by amantadine.	2003 Sep	14511008
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	15456080
Long term motor complications of levodopa: clinical features, mechanisms, and management strategies.	2004 Aug	15299154
Effects of perioperative oral amantadine on postoperative pain and morphine consumption in patients after radical prostatectomy: results of a preliminary study.	2004 Jan	14695734
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	14670755
Levetiracetam potentiates the antidyskinetic action of amantadine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of Parkinson's disease.	2004 Jul	15004218
New platinum(IV) complex with adamantylamine ligand as a promising anti-cancer drug: comparison of in vitro cytotoxic potential towards A2780/cisR cisplatin-resistant cell line within homologous series of platinum(IV) complexes.	2004 Jun	15166629
Treatment of interferon non-responsive chronic hepatitis C with triple therapy with interferon, ribavirin, and amantidine can be encouraging.	2004 Mar	14960538
[Comparative study of neurophysiological effects of adamantane derivatives in the experimental parkinsonism model].	2004 Mar-Apr	15188753
Action of celgosivir (6 O-butanoyl castanospermine) against the pestivirus BVDV: implications for the treatment of hepatitis C.	2004 May	15266896
Prevention of influenza in the general population.	2004 Nov 9	15534315
Amantadine for levodopa-induced choreic dyskinesia in compound heterozygotes for GCH1 mutations.	2004 Oct	15389992
The potential anti-hBV effect of amantadine in combination with ursodeoxycholic acid and biphenyl dimethyl dicarboxylate in hepG2 2.2.15 cells.	2005 Apr	15918519
Site-isolated porphyrin catalysts in imprinted polymers.	2005 Aug 19	15977282
Combined blockade of AMPA and NMDA glutamate receptors reduces levodopa-induced motor complications in animal models of PD.	2005 Dec	16203001
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	15652229
Preclinical anti-tumor activity of a new oral platinum(IV) drug LA-12.	2005 Jul	15930894
Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia.	2005 Jul	15899244
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Amantadine reduces the duration of levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study.	2005 Nov	16154788
Low-dose levodopa therapy in Japanese patients with Parkinson's disease: a retrospective study.	2005 Sep	16258207
Determination of serum amantadine by liquid chromatography-tandem mass spectrometry.	2005 Sep	15913590
Comparative anti-tumor efficacy of two orally administered platinum(IV) drugs in nude mice bearing human tumor xenografts.	2006 Feb	16428939
Platinum(IV) complex with adamantylamine overcomes intrinsic resistance to cisplatin in ovarian cancer cells.	2006 Jul	16364413
Interferon signal transduction of biphenyl dimethyl dicarboxylate/amantadine and anti-HBV activity in HepG2 2.2.15.	2006 May	16756086
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	16161183

Patents

Sample Use Guides

In Vivo Use Guide

Uncomplicated Influenza A Virus Illness:

Route of Administration: Oral

In Vitro Use Guide

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

Substance Class	Chemical Created by `admin` on `Sat Jun 26 07:42:45 UTC 2021` Edited by `admin` on `Sat Jun 26 07:42:45 UTC 2021`
Record UNII	9921T5P019
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMANTADINE SULFATE

Common Name

English

AMANTADINE SULPHATE (2:1)

Common Name

English

1-AMINOADAMANTANE SULPHATE

Systematic Name

English

1-ADAMANTANAMINE SULPHATE SALT (2:1)

Common Name

English

1-ADAMANTANAMINE SULFATE

Systematic Name

English

1-AMINOADAMANTANE SULFATE

Systematic Name

English

AMANTADINE SULFATE [WHO-DD]

Common Name

English

AMANTADINE SULFATE [MART.]

Common Name

English

AMANTADINE SULFATE (2:1)

Common Name

English

AMANTADINE SULPHATE

Common Name

English

AMANTADINE HEMISULFATE

Common Name

English

AMANTADINE SULFATE [MI]

Common Name

English

TRICYCLO(3.3.1.19(SUP 3,7))DECAN-1-AMINE

Common Name

English

1-ADAMANTANAMINE SULPHATE

Systematic Name

English

1-ADAMANTANAMINE SULFATE SALT (2:1)

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C281