AMANTADINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H17N
Molecular Weight	151.2491
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C1C2CC3CC1CC(C2)(C3)N

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 123 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15800186	Antagonist 2577	Parkinson's disease	10 µM [Ki]
Matrix protein 2 5 Target ID: CHEMBL1932894 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18669647	Inhibitor 7701	Influenza A virus infection

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	Matrix protein 2	Approved 7997	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	Glutamate [NMDA] receptor	Approved 7997	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

C_max

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

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

Doses

Dose	Population	Adverse events
0.8 g single, oral Overdose dose: 0.8 g route: oral experiment_type: single dose_type: Overdose co-adm with data_source: https://pubmed.ncbi.nlm.nih.gov/19135627	healthy, 2 population: healthy age: 2 sex: M food_status: n: data_source: https://pubmed.ncbi.nlm.nih.gov/19135627	Disc. AE: Status epilepticus, Agitation... AEs leading to discontinuation/dose reduction: Status epilepticus Agitation Diaphoresis Vomiting data_source: https://pubmed.ncbi.nlm.nih.gov/19135627
3000 mg single, oral Overdose dose: 3000 mg route: oral experiment_type: single dose_type: Overdose co-adm with data_source: https://pubmed.ncbi.nlm.nih.gov/3791133	unhealthy, 23 population: unhealthy age: 23 sex: M food_status: n: data_source: https://pubmed.ncbi.nlm.nih.gov/3791133	Disc. AE: CNS toxicity... AEs leading to discontinuation/dose reduction: CNS toxicity (grade 5) data_source: https://pubmed.ncbi.nlm.nih.gov/3791133
10 g single, oral Overdose dose: 10 g route: oral experiment_type: single dose_type: Overdose co-adm with data_source: https://pubmed.ncbi.nlm.nih.gov/18821491	unhealthy, 47 population: unhealthy age: 47 sex: F food_status: n: data_source: https://pubmed.ncbi.nlm.nih.gov/18821491	Disc. AE: Ventricular tachycardia... AEs leading to discontinuation/dose reduction: Ventricular tachycardia data_source: https://pubmed.ncbi.nlm.nih.gov/18821491
274 mg 1 times / day multiple, oral Recommended dose: 274 mg 1 times / day route: oral experiment_type: multiple dose_type: Recommended co-adm with data_source: https://pubmed.ncbi.nlm.nih.gov/29368539	unhealthy, 53.3 population: unhealthy age: 53.3 sex: M+F food_status: n: data_source: https://pubmed.ncbi.nlm.nih.gov/29368539	Disc. AE: Serotonin syndrome, Dry mouth... AEs leading to discontinuation/dose reduction: Serotonin syndrome (serious, 3.7%) Dry mouth (3.7%) data_source: https://pubmed.ncbi.nlm.nih.gov/29368539
274 mg 1 times / day multiple, oral Recommended dose: 274 mg 1 times / day route: oral experiment_type: multiple dose_type: Recommended co-adm with data_source: https://pubmed.ncbi.nlm.nih.gov/28604926	unhealthy, 63.9 population: unhealthy age: 63.9 sex: M+F food_status: n: data_source: https://pubmed.ncbi.nlm.nih.gov/28604926	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%) data_source: https://pubmed.ncbi.nlm.nih.gov/28604926
420 mg 1 times / day multiple, oral Highest studied dose dose: 420 mg 1 times / day route: oral experiment_type: multiple dose_type: Highest studied dose co-adm with data_source: https://pubmed.ncbi.nlm.nih.gov/25650051	unhealthy, 66.4 population: unhealthy age: 66.4 sex: M+F food_status: n: data_source: https://pubmed.ncbi.nlm.nih.gov/25650051	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%) data_source: https://pubmed.ncbi.nlm.nih.gov/25650051
100 mg 3 times / day steady, oral dose: 100 mg 3 times / day route: oral experiment_type: steady dose_type: co-adm with data_source: https://clinicaltrials.gov/ct2/show/NCT01071395	unhealthy population: unhealthy age: sex: food_status: n: data_source: https://clinicaltrials.gov/ct2/show/NCT01071395	Other AEs: Dry mouth... Other AEs: Dry mouth (below serious, 4 patients) data_source: https://clinicaltrials.gov/ct2/show/NCT01071395

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1470 inhibitor 1172	substrate 865 inhibitor 1318	substrate 1038 inhibitor 1421

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1268 CYP2B6 679 CYP2C19 1215 CYP2C8 761 CYP2E1 761 CYP3A5 66 OCT1 473 OCT2 582 OCT3 139 MATE1 290 MATE2 258	CYP1A2 892 CYP2B6 575 CYP2C19 830 CYP2C8 586 CYP2E1 567 CYP3A5 346 OCT2 304

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1406	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2B6 845	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2C19 1277	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2C8 810	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2C9 1362	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2D6 1455	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2E1 841	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP3A4 1462	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP3A5 119	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
MATE1 291	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 111.8 uM]
MATE2 258	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 1167 uM]
OCT1 488	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 236 uM]
OCT2 583	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 284 uM]
OCT3 139	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki >1000 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 892	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2B6 575	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2C19 830	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2C8 586	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2C9 865	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2D6 1038	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP2E1 567	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP3A4 1470	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
CYP3A5 346	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10	unlikely
OCT2 304	substrate 2752 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
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
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
[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
Mirtazapine in L-dopa-induced dyskinesias.	2003 Jul-Aug	12897636
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
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
Effects of perioperative oral amantadine on postoperative pain and morphine consumption in patients after radical prostatectomy: results of a preliminary study.	2004 Jan	14695734
Motor-learning impairment by amantadine in healthy volunteers.	2004 Jan	14532914
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
Platinum(IV) complex with adamantylamine as nonleaving amine group: synthesis, characterization, and in vitro antitumor activity against a panel of cisplatin-resistant cancer cell lines.	2004 Jan 29	14736257
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
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
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
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
Glutamate receptors in neuroinflammatory demyelinating disease.	2006	16883070
Comparative anti-tumor efficacy of two orally administered platinum(IV) drugs in nude mice bearing human tumor xenografts.	2006 Feb	16428939
[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
Platinum(IV) complex with adamantylamine overcomes intrinsic resistance to cisplatin in ovarian cancer cells.	2006 Jul	16364413
Amantadine-induced livedo reticularis: a report of two cases.	2006 Mar	16573266
Hiccups associated with dopamine agonists in Parkinson disease.	2006 Mar 14	16534128
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
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:

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

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

NSC-341865

Code

English

AMANTIDINE

Common Name

English

AMANTADINE [WHO-DD]

Common Name

English

AMANTADINE [HSDB]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C93038