RIMANTADINE

First approved in 1993

Details

Stereochemistry	RACEMIC
Molecular Formula	C12H21N
Molecular Weight	179.3018
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(N)C12CC3CC(CC(C3)C1)C2

InChI

InChIKey=UBCHPRBFMUDMNC-UHFFFAOYSA-N

InChI=1S/C12H21N/c1-8(13)12-5-9-2-10(6-12)4-11(3-9)7-12/h8-11H,2-7,13H2,1H3

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019649s015lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB00478 | http://reference.medscape.com/drug/flumadine-rimantadine-342626 | https://www.drugs.com/drug-interactions/rimantadine.html | https://www.ncbi.nlm.nih.gov/pubmed/3346834

Rimantadine (INN, sold under the trade name Flumadine) is an orally administered antiviral drug used to treat, and in rare cases prevent, influenzavirus A infection. Rimantadine is an M2 ion channel inhibitor which specifically inhibits the replication of influenza A viruses by interfering with the uncoating process of the virus. M2 inhibitors block the ion channel formed by the M2 protein that spans the viral membrane (Hay 1985, Sugrue 1991). The influenza virus enters its host cell by receptor-mediated endocytosis. Thereafter, acidification of the endocytotic vesicles is required for the dissociation of the M1 protein from the ribonucleoprotein complexes. Only then are the ribonucleoprotein particles imported into the nucleus via the nuclear pores. The hydrogen ions needed for acidification pass through the M2 channel. The drug is effective against all influenza A subtypes that have previously caused disease in humans (H1N1, H2N2, and H3N2), but not against influenza B virus because the M2 protein is unique to influenza A viruses. Rimantadine is not active against the avian flu subtype H5N1 strains that have recently caused disease in humans.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Matrix protein 2 5 Target ID: CHEMBL1772930 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25342196	Inhibitor 8297
Solute carrier family 22 member 2 8 Target ID: CHEMBL1743122 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23241029	Inhibitor 8297		4.4 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Influenza A virus infection 9 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019649s015lbl.pdf	Curative		Approved 8429	FLUMADINE Approved Use Rimantadine hydrochloride tablet is indicated for the prophylaxis and treatment of illness caused by various strains of influenza A virus in adults (17 years and older). Rimantadine hydrochloride tablet is indicated for prophylaxis against influenza A virus in children (1 year to 16 years of age). PROPHYLAXIS In controlled studies of children (1 year to 16 years of age), healthy adults (17 years and older), and elderly patients (65 years of age and older), rimantadine hydrochloride has been shown to be safe and effective in preventing signs and symptoms of infection caused by various strains of influenza A virus. Since rimantadine hydrochloride does not completely prevent the host immune response to influenza A infection, individuals who take this drug may still develop immune responses to natural disease or vaccination and may be protected when later exposed to antigenically-related viruses. Following vaccination during an influenza outbreak, rimantadine hydrochloride prophylaxis should be considered for the 2 to 4 week time period required to develop an antibody response. However, the safety and effectiveness of rimantadine hydrochloride prophylaxis have not been demonstrated for longer than 6 weeks. TREATMENT Rimantadine hydrochloride therapy should be considered for adults (17 years and older) who develop an influenza-like illness during known or suspected influenza A infection in the community. When administered within 48 hours after onset of signs and symptoms of infection caused by influenza A virus strains, rimantadine hydrochloride has been shown to reduce the duration of fever and systemic symptoms. The following points should be considered before initiating treatment or prophylaxis with rimantadine hydrochloride: Rimantadine hydrochloride is not a substitute for early vaccination on an annual basis as recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices Influenza viruses change over time. Emergence of resistance mutations could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use rimantadine hydrochloride. Launch Date 1993
Respiratory tract infections 85 Sources: https://clinicaltrials.gov/ct2/show/NCT01055990	Curative		Phase II 1132	FLUMADINE Approved Use Rimantadine hydrochloride tablet is indicated for the prophylaxis and treatment of illness caused by various strains of influenza A virus in adults (17 years and older). Rimantadine hydrochloride tablet is indicated for prophylaxis against influenza A virus in children (1 year to 16 years of age). PROPHYLAXIS In controlled studies of children (1 year to 16 years of age), healthy adults (17 years and older), and elderly patients (65 years of age and older), rimantadine hydrochloride has been shown to be safe and effective in preventing signs and symptoms of infection caused by various strains of influenza A virus. Since rimantadine hydrochloride does not completely prevent the host immune response to influenza A infection, individuals who take this drug may still develop immune responses to natural disease or vaccination and may be protected when later exposed to antigenically-related viruses. Following vaccination during an influenza outbreak, rimantadine hydrochloride prophylaxis should be considered for the 2 to 4 week time period required to develop an antibody response. However, the safety and effectiveness of rimantadine hydrochloride prophylaxis have not been demonstrated for longer than 6 weeks. TREATMENT Rimantadine hydrochloride therapy should be considered for adults (17 years and older) who develop an influenza-like illness during known or suspected influenza A infection in the community. When administered within 48 hours after onset of signs and symptoms of infection caused by influenza A virus strains, rimantadine hydrochloride has been shown to reduce the duration of fever and systemic symptoms. The following points should be considered before initiating treatment or prophylaxis with rimantadine hydrochloride: Rimantadine hydrochloride is not a substitute for early vaccination on an annual basis as recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices Influenza viruses change over time. Emergence of resistance mutations could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use rimantadine hydrochloride. Launch Date 1993

C_max

Value	Dose	Analyte	Population
74 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019649s015lbl.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	RIMANTADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
416 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3606083/	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RIMANTADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
181 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3606083/	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RIMANTADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
20300 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3606083/	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:		RIMANTADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
8170 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3606083/	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:		RIMANTADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
25.4 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019649s015lbl.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	RIMANTADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
33 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3606083/	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RIMANTADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
26 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3606083/	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RIMANTADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
60% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019649s015lbl.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		RIMANTADINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7347558/	healthy, 32.1 n = 64 Health Status: healthy Age Group: 32.1 Sex: M+F Population Size: 64 Sources: https://pubmed.ncbi.nlm.nih.gov/7347558/	Sources: https://pubmed.ncbi.nlm.nih.gov/7347558/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 MATE1 306 MATE2 263 OCT2 647	UGT 192

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32658735/	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32658735/	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32658735/	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32658735/	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32658735/	no
MATE1 308	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23241029/	yes
MATE2 263	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23241029/	yes
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23241029/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
UGT 192	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/3252751/	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY518437	https://www.001chemical.com/chem/13392-28-4
001 Chemical	DY577788	https://www.001chemical.com/chem/887336-05-2
001 Chemical	DY577789	https://www.001chemical.com/chem/887336-06-3
AA Blocks	AA00HT0M	https://www.aablocks.com/goods/Goods/detail?id=AA00HT0M
AHH Chemical co.,ltd	MR-1013893	http://www.ahhchemical.com/product/MR-1013893.html
AK Scientific, Inc. (AKSCI)	71879	http://www.aksci.com/item_detail.php?cat=71879
Aaron Chemicals	AR00HTSE	http://www.aaronchem.com/13392-28-4
AbMole Bioscience	M5931	http://www.abmole.com/products/rimantadine.html
Achemtek	0104-023050	http://www.achemtek.com/13392-28-4
Alinda	ALBB-013870	http://alinda.ru/finechem_en_.html?i=ALBB-013870
Ambinter	Amb17938007	http://www.ambinter.com/reference/17938007
Ambinter	Amb24404900	http://www.ambinter.com/reference/24404900
Ambinter	Amb24548260	http://www.ambinter.com/reference/24548260
Ambinter	Amb25090834	http://www.ambinter.com/reference/25090834
Ambinter	Amb2564389	http://www.ambinter.com/reference/2564389
Angel Pharmatech	AG307433	http://www.angelpharmatech.com/13392-28-4.html
Angene	AGN-PC-0PK5FE	http://www.angenechemical.com/productshow/AGN-PC-0PK5FE.html
Anward	ANW-72018	http://www.anward.com/pro_result/58469
Aurora Fine Chemicals LLC	A00.495.472	http://online.aurorafinechemicals.com/info?ID=A00.495.472
Aurum Pharmatech LLC	H6325	http://www.Aurumpharmatech.com/Product/ProductDetails/H6325
BioChemPartner	BCP12269	http://www.biochempartner.com/13392-28-4-BCP12269
BioCrick	BCC4938	http://www.biocrick.com/Rimantadine-BCC4938.html
Chem Scene	CS-2380	http://www.chemscene.com/13392-28-4.html
Chemenu	CM132183	http://www.chemenu.com/products/CM132183
Chemspace	CSSB00000181832	https://chem-space.com/CSSB00000181832
Debye Scientific	DB-042207	http://www.debyesci.com/cas_13392-28-4.html
Enamine	Z56757137	https://www.enaminestore.com/catalog/Z56757137
Finetech	FT-0630403	http://www.finetechnology-ind.com/prod/detail/pub/13392-28-4.html
Hairui	HR131337	http://www.hairuichem.com/en/product/13392-28-4.html
Lab Network	LN00248351	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00248351
MedChem Express	HY-B0338	https://www.medchemexpress.com/rimantadine.html
Molcore	MC518437	https://www.molcore.com/product/13392-28-4
Molcore	MC577788	https://www.molcore.com/product/887336-05-2
Molcore	MC577789	https://www.molcore.com/product/887336-06-3
MuseChem	I001300	https://www.musechem.com/product/I001300.html
OChem	7365	http://www.ocheminc.com/index.php?act=psearch&pid=392R284
Oakwood	38266	http://www.oakwoodchemical.com/p-42085-038266.aspx
THE BioTek	bt-253371	https://www.thebiotek.com/product/inhibitors/bt-253371
mcule	MCULE-9027470290	https://mcule.com/MCULE-9027470290/

PubMed

Title	Date	PubMed
Antiviral agents. 2. Structure-activity relationships of compounds related to 1-adamantanamine.	1971 Jun	5091970
Influence of membrane (M) protein on influenza A virus virion transcriptase activity in vitro and its susceptibility to rimantadine.	1980 Feb	6893343
Enhancement of activity against influenza viruses by combinations of antiviral agents.	1980 Oct	7447417
Comparative toxicity of amantadine hydrochloride and rimantadine hydrochloride in healthy adults.	1981 Feb	7347558
Combined interferon-alpha 2, rimantadine hydrochloride, and ribavirin inhibition of influenza virus replication in vitro.	1984 Jan	6703684
Rimantadine and seizures.	1989 Feb 15	2913918
Comparative anti-influenza virus activity of 2'-deoxy-2'-fluororibosides in vitro.	1993 Aug	8215305
4-Guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid is a highly effective inhibitor both of the sialidase (neuraminidase) and of growth of a wide range of influenza A and B viruses in vitro.	1993 Jul	8363379
Susceptibilities to rimantadine of influenza A/H1N1 and A/H3N2 viruses isolated during the epidemics of 1988 to 1989 and 1989 to 1990.	1993 Oct	8257151
What should we advise about adjunctive therapies, including herbal medicines, for hepatitis C?	2000 May	10921401
A rapid assay for evaluation of antiviral activity against coxsackie virus B3, influenza virus A, and herpes simplex virus type 1.	2001 Jun	11377720
Heterocyclic rimantadine analogues with antiviral activity.	2003 Dec 1	14642592
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
Heterocyclic rimantadine analogues with antiviral activity.	2006 May 15	16439137
Potentiation of azole antifungals by 2-adamantanamine.	2013 Aug	23689724

Patents

Sample Use Guides

In Vivo Use Guide

100 mg PO q12hr preferably within 48 hours after onset of signs and symptoms of influenza A infection

Route of Administration: Oral

In Vitro Use Guide

The rimantadine_resistant variant of influenza virus A/Aichi/68 was obtained as follows. Initially the ED50 value was 0.612 μg/mL, which ensured the inhibition of viral hemagglutinin formation and more than 50% prevention of the development of the virus induced cytopathic effect (CPE). This virus was passaged three times in MDCK cells in the presence of increasing concentrations of rimantadine hydrochloride. Its final concentration was 50 μg/mL. Reproduction of influenza virus in cells MDCK (infectious titer) is not inhibited by the drug at a concentration of 25–50 μg/mL. This virus was denoted by us as A/Aichi/68/Rr.Initially, influenza viruses A/H5N1 and A/H1N1pdm09 were also resistant to rimantadine. Their infectious titer was not inhibited by rimantadine at a concentration of 25 μg/mL.

Name

Type

Language

RIMANTADINE

Official Name

English

rimantadine [INN]

Common Name

English

RIMANTADINE [HSDB]

Common Name

English

(RS)-1-(1-ADAMANTYL)ETHANAMINE

Systematic Name

English

RIMANTADINE [MI]

Common Name

English

RIMANTADINE [VANDF]

Common Name

English

Rimantadine [WHO-DD]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175543