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 2778		10.0 µM [Ki]
Matrix protein 2 5 Target ID: CHEMBL1932894 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18669647	Inhibitor 8297

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 8429	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 226 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6e6e111-38da-43a2-b6c4-15e69b720495	Primary		Approved 8429	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
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 Route: single Dose: 0.8 g Sources: https://pubmed.ncbi.nlm.nih.gov/19135627 Page: p.120	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/19135627 Page: p.120	Disc. AE: Status epilepticus, Agitation... AEs leading to discontinuation/dose reduction: Status epilepticus Agitation Diaphoresis Vomiting Sources: https://pubmed.ncbi.nlm.nih.gov/19135627 Page: p.120
3000 mg single, oral Overdose Dose: 3000 mg Route: oral Route: single Dose: 3000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3791133 Page: p.757	unhealthy, 23 n = 1 Health Status: unhealthy Condition: Schizophrenia Age Group: 23 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3791133 Page: p.757	Disc. AE: CNS toxicity... AEs leading to discontinuation/dose reduction: CNS toxicity (grade 5) Sources: https://pubmed.ncbi.nlm.nih.gov/3791133 Page: p.757
10 g single, oral Overdose Dose: 10 g Route: oral Route: single Dose: 10 g Co-administed with:: diphenhydramine, p.o(250 mg, single) Sources: https://pubmed.ncbi.nlm.nih.gov/18821491 Page: p.174	unhealthy, 47 n = 1 Health Status: unhealthy Condition: Schizophrenia Age Group: 47 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18821491 Page: p.174	Disc. AE: Ventricular tachycardia... AEs leading to discontinuation/dose reduction: Ventricular tachycardia Sources: https://pubmed.ncbi.nlm.nih.gov/18821491 Page: p.174
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: https://pubmed.ncbi.nlm.nih.gov/29368539 Page: p.605	unhealthy, 53.3 n = 27 Health Status: unhealthy Condition: Multiple sclerosis Age Group: 53.3 Sex: M+F Population Size: 27 Sources: https://pubmed.ncbi.nlm.nih.gov/29368539 Page: p.605	Disc. AE: Serotonin syndrome, Dry mouth... AEs leading to discontinuation/dose reduction: Serotonin syndrome (serious, 3.7%) Dry mouth (3.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/29368539 Page: p.605
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: https://pubmed.ncbi.nlm.nih.gov/28604926	unhealthy, 63.9 n = 63 Health Status: unhealthy Condition: Levodopa-Induced Dyskinesia in Parkinson Disease Age Group: 63.9 Sex: M+F Population Size: 63 Sources: 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%) Sources: 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 Route: multiple Dose: 420 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25650051 Page: p.793	unhealthy, 66.4 n = 20 Health Status: unhealthy Condition: Levodopa-Induced Dyskinesia in Parkinson Disease Age Group: 66.4 Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/25650051 Page: p.793	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: https://pubmed.ncbi.nlm.nih.gov/25650051 Page: p.793
100 mg 3 times / day steady, oral Dose: 100 mg, 3 times / day Route: oral Route: steady Dose: 100 mg, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01071395	unhealthy n = 36 Health Status: unhealthy Condition: Parkinson's disease Population Size: 36 Sources: https://clinicaltrials.gov/ct2/show/NCT01071395	Other AEs: Dry mouth... Other AEs: Dry mouth (below serious, 4 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01071395

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C19 1478 CYP2C8 911 CYP2E1 882 CYP3A5 73 OCT1 512 OCT2 647 OCT3 150 MATE1 306 MATE2 263	CYP1A2 1054 CYP2B6 664 CYP2C19 991 CYP2C8 693 CYP2E1 667 CYP3A5 395 OCT2 355

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP3A5 130	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
MATE1 308	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 111.8 uM]
MATE2 263	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 1167 uM]
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 236 uM]
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 284 uM]
OCT3 150	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki >1000 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP3A5 395	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
OCT2 355	substrate 3367 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
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
eMolecules	27515804	https://www.emolecules.com/cgi-bin/more?vid=27515804
eMolecules	476391	https://www.emolecules.com/cgi-bin/more?vid=476391

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
Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.	1992 Sep	1416885
Medication-induced hallucination and cerebral blood flow in Parkinson's disease.	1999 May	10399867
Amantadine-induced peripheral neuropathy.	1999 Nov 10	10563642
[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
[Worsened orthostatic hypotension due to levodopa administration in a case of Parkinson's disease].	2000 Mar	10879077
Cerebellar Ataxia.	2000 May	11096749
Beneficial effects of amantadine on L-dopa-induced dyskinesias in Parkinson's disease.	2000 Sep	11009193
Quetiapine for l-dopa-induced psychosis in PD.	2000 Sep 26	10994027
Novel 3-(2-adamantyl)pyrrolidines with potent activity against influenza A virus-identification of aminoadamantane derivatives bearing two pharmacophoric amine groups.	2001 Aug 20	11514155
A rapid assay for evaluation of antiviral activity against coxsackie virus B3, influenza virus A, and herpes simplex virus type 1.	2001 Jun	11377720
Synthesis and pharmacological evaluation of potent and enantioselective sigma 1, and sigma 2 ligands.	2001 Mar	11409325
An MCASE approach to the search of a cure for Parkinson's Disease.	2002 Apr 2	11926966
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
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
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
Motor-learning impairment by amantadine in healthy volunteers.	2004 Jan	14532914
Improved neurological function after Amantadine treatment in two patients with brain injury.	2005 Apr	15769570
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
Comparative anti-tumor efficacy of two orally administered platinum(IV) drugs in nude mice bearing human tumor xenografts.	2006 Feb	16428939
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
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

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