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

Molecular Formula	C10H17N
Molecular Weight	151.2487
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

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate [NMDA] receptor 123 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15800186	Antagonist 2737		10.0 µM [Ki]
Matrix protein 2 5 Target ID: CHEMBL1932894 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18669647	Inhibitor 8146

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 8307	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 5.40518384E11
Parkinson's disease 223 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6e6e111-38da-43a2-b6c4-15e69b720495	Primary		Approved 8307	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 5.40518384E11

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 1670 inhibitor 1532	substrate 985 inhibitor 1695	substrate 1168 inhibitor 1789

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1463 CYP2B6 770 CYP2C19 1410 CYP2C8 869 CYP2E1 846 CYP3A5 73 OCT1 498 OCT2 630 OCT3 143 MATE1 302 MATE2 259	CYP1A2 1013 CYP2B6 648 CYP2C19 955 CYP2C8 670 CYP2E1 633 CYP3A5 383 OCT2 336

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1620	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2B6 946	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C19 1484	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C8 923	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C9 1747	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2D6 1826	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2E1 929	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP3A4 1857	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP3A5 130	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
MATE1 304	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 111.8 uM]
MATE2 259	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 1167 uM]
OCT1 513	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 236 uM]
OCT2 631	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki 284 uM]
OCT3 143	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16581093/	yes [Ki >1000 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1013	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2B6 648	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C19 955	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C8 670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2C9 985	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2D6 1168	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP2E1 633	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP3A4 1670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
CYP3A5 383	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	unlikely
OCT2 336	substrate 3264 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
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
Neuroleptic malignant syndrome induced by haloperidol following traumatic brain injury.	1999 Dec	10628507
Amantadine-induced peripheral neuropathy.	1999 Nov 10	10563642
The role of glutamatergic transmission in the pathogenesis of levodopa-induced dyskinesias. Potential therapeutic approaches.	2001	12001656
A rapid assay for evaluation of antiviral activity against coxsackie virus B3, influenza virus A, and herpes simplex virus type 1.	2001 Jun	11377720
Intravenous amantadine improves levadopa-induced dyskinesias: an acute double-blind placebo-controlled study.	2001 May	11391748
[Effect of the new potential anti-Parkinson agent, hymantane, on levels of monoamines and their metabolites in rat striatum (a microdialysis study)].	2001 Nov-Dec	11871228
An MCASE approach to the search of a cure for Parkinson's Disease.	2002 Apr 2	11926966
Chiral separation of enantiomeric 1,2-diamines using molecular imprinting method and selectivity enhancement by addition of achiral primary amines into eluents.	2002 Jan	11817724
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
Long term motor complications of levodopa: clinical features, mechanisms, and management strategies.	2004 Aug	15299154
Prevention of influenza in the general population.	2004 Nov 9	15534315
Improved neurological function after Amantadine treatment in two patients with brain injury.	2005 Apr	15769570
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
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
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
Amantadine-induced livedo reticularis: a report of two cases.	2006 Mar	16573266
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
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

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

Substance Class	Chemical Created by `admin` on `Fri Dec 16 16:36:54 UTC 2022` Edited by `admin` on `Fri Dec 16 16:36:54 UTC 2022`
Record UNII	BF4C9Z1J53
Record Status	`Validated (UNII)`
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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