AMANTADINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H17N
Molecular Weight	151.2487
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC12CC3CC(CC(C3)C1)C2

InChI

InChIKey=DKNWSYNQZKUICI-UHFFFAOYSA-N

InChI=1S/C10H17N/c11-10-4-7-1-8(5-10)3-9(2-7)6-10/h7-9H,1-6,11H2

HIDE SMILES / InChI

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

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate [NMDA] receptor 125 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15800186	Antagonist 2849		10.0 µM [Ki]
Matrix protein 2 5 Target ID: CHEMBL1932894 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18669647	Inhibitor 8504

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 8583	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 1987
Parkinson's disease 232 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6e6e111-38da-43a2-b6c4-15e69b720495	Primary		Approved 8583	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 1987

C_max

Value	Dose	Co-administered	Analyte	Population
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
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

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

T_1/2

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

F_unbound

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 1946 inhibitor 2252	substrate 1193 inhibitor 2438	substrate 1388 inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2B6 926 CYP2C19 2057 CYP2C8 1057 CYP2E1 1060 CYP3A5 136 OCT1 620 OCT2 779 OCT3 159 MATE1 415 MATE2 267	CYP1A2 1197 CYP2B6 776 CYP2C19 1119 CYP2C8 810 CYP2E1 729 CYP3A5 446 OCT2 434

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP3A5 201	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
MATE1 416	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 111.8 uM]
MATE2 267	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 1167 uM]
OCT1 656	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 236 uM]
OCT2 782	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 284 uM]
OCT3 161	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki >1000 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2E1 729	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP3A5 446	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
OCT2 434	substrate 4014 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
ChemicalBook	CB3259991	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3259991
eMolecules	27515804	https://www.emolecules.com/cgi-bin/more?vid=27515804
eMolecules	476391	https://www.emolecules.com/cgi-bin/more?vid=476391
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
Blockade of the central effects of d-amphetamine by amantadine. II.	1975 May	1242323
Efficacy of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide against influenza virus infections in mice.	1975 May	1147589
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	1725692
Neurotoxicity of chlorpromazine and modulation by amantadine as a function of mouse strain.	1991 Fall	1745440
A trigger for Tourette's syndrome.	1992 Mar	1564044
Medication-induced hallucination and cerebral blood flow in Parkinson's disease.	1999 May	10399867
Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study.	1999 Nov	10555659
[Amantadine for the treatment of levodopa dyskinesias in Parkinson's disease].	2000	11050808
Amantadine-induced multiple spike waves on an electroencephalogram of a schizophrenic patient.	2000 Jan	12611370
The effect of amantadine on levodopa-induced dyskinesias in Parkinson's disease: a double-blind, placebo-controlled study.	2000 Mar-Apr	10803797
Addition of hydrophilic and lipophilic compounds of biological relevance to the monoolein/water system. I. Phase behavior.	2001 Jan	11163344
Amantadine-induced cortical myoclonus.	2001 Jan 23	11160978
A rapid assay for evaluation of antiviral activity against coxsackie virus B3, influenza virus A, and herpes simplex virus type 1.	2001 Jun	11377720
[L-dopa-induced movement disorders in Parkinson disease. Amantadine improves dyskinesia].	2001 May 28	11434272
Synthesis of valproic acid amides of a melatonin derivative, a piracetam and amantadine for biological tests.	2001 Oct	11700961
[The use of amantadine sulfate in combined therapy of Parkinson's disease].	2002	12161861
Comparison of colorimetric, fluorometric, and visual methods for determining anti-influenza (H1N1 and H3N2) virus activities and toxicities of compounds.	2002 Oct	12367731
Amantadine in Huntington's disease: open-label video-blinded study.	2002 Sep	12548355
Synthesis and antioxidant activity evaluation of novel antiparkinsonian agents, aminoadamantane derivatives of nitroxyl free radical.	2003 Aug 5	12878145
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
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
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
Bitterness evaluation of medicines for pediatric use by a taste sensor.	2004 Aug	15304986
Long term motor complications of levodopa: clinical features, mechanisms, and management strategies.	2004 Aug	15299154
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
Adverse effects of amantadine and oseltamivir used during respiratory outbreaks in a center for developmentally disabled adults.	2004 Nov	15566030
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
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
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Determination of serum amantadine by liquid chromatography-tandem mass spectrometry.	2005 Sep	15913590
Glutamate receptors in neuroinflammatory demyelinating disease.	2006	16883070
[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	16915929
The pharmacology of aminoadamantane nitrates.	2006 Jul	16842096
Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson's disease.	2006 Nov	16960862
Behavioral effects of aminoadamantane class NMDA receptor antagonists on schedule-induced alcohol and self-administration of water in mice.	2006 Sep	16835770
Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line.	2006 Sep 15	16978399
Modulation of L-DOPA-induced abnormal involuntary movements by clinically tested compounds: further validation of the rat dyskinesia model.	2007 Apr 16	17306893
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	17502147

Patents

Sample Use Guides

In Vivo Use Guide

Uncomplicated Influenza A Virus Illness: Adult: 200 mg; two 100 mg capsules as a single daily dose. The daily dosage may be split into one capsule of 100 mg twice a day. In persons 65 years of age or older, the daily dosage is 100 mg. Parkinsonism: Adult: is 100 mg twice a day when used alone. Amantadine Hydrochloride Capsules have an onset of action usually within 48 hours. The initial dose is 100 mg daily for patients with serious associated medical illnesses or who are receiving high doses of other antiparkinson drugs. After one to several weeks at 100 mg once daily, the dose may be increased to 100 mg twice daily, if necessary.

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

Name

Type

Language

AMANTADINE

Official Name

English

NSC-341865

Preferred Name

English

GOCOVRI

Brand Name

English

AMANTADINE [MI]

Common Name

English

AMANTADINE [MART.]

Common Name

English

AMANTADINE [VANDF]

Common Name

English

ADAMANTAN-1-AMINE

Systematic Name

English

amantadine [INN]

Common Name

English

AMANTIDINE

Common Name

English

Amantadine [WHO-DD]

Common Name

English

AMANTADINE [HSDB]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C93038