Jump to section

References

Trials

Economics

Properties

Spectra

Taxonomy

Rimantadine

Targets (1)

Identification

Name

Rimantadine

Accession Number

DB00478 (APRD01219)

Type

Small Molecule

Groups

Approved, Investigational

Description

An RNA synthesis inhibitor that is used as an antiviral agent in the prophylaxis and treatment of influenza.

Structure

Similar Structures

Synonyms

alpha-Methyl-1-adamantanemethylamine
alpha-Methyladamantanemethylamine
Rimantadina
Rimantadine
Rimantadinum

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Rimantadine hydrochloride	JEI07OOS8Y	1501-84-4	OZBDFBJXRJWNAV-UHFFFAOYSA-N

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Flumadine	Syrup	50 mg/5mL	Oral	FOREST PHARMACEUTICALS, INC.	2007-07-10	Not applicable
Flumadine	Tablet	100 mg/1	Oral	FOREST PHARMACEUTICALS, INC.	2007-07-10	Not applicable
Flumadine	Tablet	100 mg/1	Oral	Physicians Total Care, Inc.	2009-09-22	2010-06-30
Flumadine	Tablet	100 mg/1	Oral	Caraco Pharma, Inc.	2009-09-22	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Rimantadine Hydrochloride	Tablet, film coated	100 mg/1	Oral	Sandoz	2001-11-02	2012-03-31
Rimantadine Hydrochloride	Tablet, film coated	100 mg/1	Oral	A-S Medication Solutions	2005-04-01	Not applicable
Rimantadine Hydrochloride	Tablet, film coated	100 mg/1	Oral	Carilion Materials Management	2005-04-01	Not applicable
Rimantadine Hydrochloride	Tablet, film coated	100 mg/1	Oral	H.J. Harkins Company	2005-04-01	Not applicable
Rimantadine Hydrochloride	Tablet, film coated	100 mg/1	Oral	bryant ranch prepack	2005-04-01	Not applicable
Rimantadine Hydrochloride	Tablet, film coated	100 mg/1	Oral	Impax Generics	2005-04-01	Not applicable
Rimantadine Hydrochloride	Tablet, film coated	100 mg/1	Oral	Stat Rx USA	2005-04-01	Not applicable

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Rimantalist	Rimantadine hydrochloride (100 mg/1) + L-Arginine (60 mg/1)	Kit		Physician Therapeutics Llc	2011-07-07	Not applicable

Categories

UNII

0T2EF4JQTU

CAS number

13392-28-4

Weight

Average: 179.3018
Monoisotopic: 179.167399677

Chemical Formula

C₁₂H₂₁N

InChI Key

UBCHPRBFMUDMNC-UHFFFAOYSA-N

InChI

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

IUPAC Name

1-(adamantan-1-yl)ethan-1-amine

SMILES

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

Pharmacology

Indication

For the prophylaxis and treatment of illness caused by various strains of influenza A virus in adults.

Associated Conditions

Influenza A Virus Infection

Pharmacodynamics

Rimantadine, a cyclic amine, is a synthetic antiviral drug and a derivate of adamantane, like a similar drug amantadine. Rimantadine is inhibitory to the in vitro replication of influenza A virus isolates from each of the three antigenic subtypes (H1N1, H2H2 and H3N2) that have been isolated from man. Rimantadine has little or no activity against influenza B virus. Rimantadine does not appear to interfere with the immunogenicity of inactivated influenza A vaccine.

Mechanism of action

The mechanism of action of rimantadine is not fully understood. Rimantadine appears to exert its inhibitory effect early in the viral replicative cycle, possibly inhibiting the uncoating of the virus. Genetic studies suggest that a virus protein specified by the virion M2 gene plays an important role in the susceptibility of influenza A virus to inhibition by rimantadine.

Target	Actions	Organism
AMatrix protein 2	other/unknown	Influenza A virus (strain A/Ann Arbor/6/1960 H2N2)

Absorption

Well absorbed, with the tablet and syrup formulations being equally absorbed after oral administration.

Volume of distribution

Not Available

Protein binding

Approximately 40% over typical plasma concentrations.

Metabolism

Following oral administration, rimantadine is extensively metabolized in the liver with less than 25% of the dose excreted in the urine as unchanged drug. Glucuronidation and hydroxylation are the major metabolic pathways.

Route of elimination

Following oral administration, rimantadine is extensively metabolized in the liver with less than 25% of the dose excreted in the urine as unchanged drug.

Half life

25 to 30 hours in young adults (22 to 44 years old). Approximately 32 hours in elderly (71 to 79 years old) and in patients with chronic liver disease. Approximately 13 to 38 hours in children (4 to 8 years old).

Clearance

Not Available

Toxicity

Oral LD₅₀ in rats is 640 mg/kg. Overdoses of a related rug, amantadine, have been reported with adverse reactions consisting of agitation, hallucinations, cardiac arrhythmia and death.

Affected organisms

Human Influenza A Virus

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
Influenza a virus a/california/7/2009 (h1n1) live (attenuated) antigen	The therapeutic efficacy of Influenza a virus a/california/7/2009 (h1n1) live (attenuated) antigen can be decreased when used in combination with Rimantadine.
Influenza a virus a/perth/16/2009 (h3n2) live (attenuated) antigen	The therapeutic efficacy of Influenza a virus a/perth/16/2009 (h3n2) live (attenuated) antigen can be decreased when used in combination with Rimantadine.
Influenza Vaccine (Live/Attenuated)	The therapeutic efficacy of Influenza Vaccine (Live/Attenuated) can be decreased when used in combination with Rimantadine.
Varicella Zoster Vaccine (Live/Attenuated)	The therapeutic efficacy of Varicella Zoster Vaccine (Live/Attenuated) can be decreased when used in combination with Rimantadine.

Food Interactions

Not Available

References

Synthesis Reference

US3352912

General References

Not Available

External Links

Human Metabolome Database: HMDB0014621
KEGG Drug: D08483
KEGG Compound: C07236
PubChem Compound: 5071
PubChem Substance: 46505973
ChemSpider: 4893
BindingDB: 50216627
ChEBI: 94440
ChEMBL: CHEMBL959
Therapeutic Targets Database: DAP001087
PharmGKB: PA164748038
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Rimantadine

ATC Codes

J05AC02 — Rimantadine

FDA label

Download (62.4 KB)

MSDS

Download (62.7 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Healthy Volunteers	1
2	Completed	Not Available	Hepatitis C Viral Infection	1

Pharmacoeconomics

Manufacturers

Forest laboratories inc
Caraco pharmaceutical laboratories ltd
Actavis totowa llc
Corepharma llc
Impax laboratories inc

Packagers

Caraco Pharmaceutical Labs
Corepharma LLC
Dispensing Solutions
Diversified Healthcare Services Inc.
Forest Pharmaceuticals
Global Pharmaceuticals
H.J. Harkins Co. Inc.
Impax Laboratories Inc.
Inwood Labs
McNeil Laboratories
Medisca Inc.
Nucare Pharmaceuticals Inc.
Ortho-McNeil-Janssen Pharmaceuticals Inc.
PD-Rx Pharmaceuticals Inc.
Physicians Total Care Inc.
Prescript Pharmaceuticals
Sandoz
Southwood Pharmaceuticals
Vistakon Pharmaceuticals LLC

Dosage forms

Form	Route	Strength
Syrup	Oral	50 mg/5mL
Tablet	Oral	100 mg/1
Tablet, film coated	Oral	100 mg/1
Kit

Prices

Unit description	Cost	Unit
Levofloxacin hemihydr 100% powder	42.69USD	g
Levaquin 750 mg leva-pak tablet	27.51USD	tablet
Levaquin 750 mg tablet	27.51USD	tablet
Iquix 1.5% eye drops	15.71USD	ml
Levaquin 500 mg tablet	14.69USD	tablet
Levaquin 250 mg tablet	14.09USD	tablet
Quixin 0.5% eye drops	12.21USD	ml
Rimantadine hcl 100 mg tablet	2.44USD	tablet
Flumadine 100 mg tablet	2.4USD	tablet
Levaquin i.v. 25 mg/ml vial	1.94USD	ml
Levaquin 500 mg/100 ml d5w	0.44USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	>300 °C	Not Available
water solubility	Hydrochloride salt freely soluble (50 mg/ml at 20 °C)	Not Available
logP	3.6	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.00915 mg/mL	ALOGPS
logP	3.28	ALOGPS
logP	2.22	ChemAxon
logS	-4.3	ALOGPS
pKa (Strongest Basic)	10.14	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	1	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	26.02 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	54.52 m³·mol^-1	ChemAxon
Polarizability	21.79 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	1.0
Blood Brain Barrier	+	0.9798
Caco-2 permeable	+	0.6348
P-glycoprotein substrate	Non-substrate	0.6811
P-glycoprotein inhibitor I	Non-inhibitor	0.8751
P-glycoprotein inhibitor II	Non-inhibitor	0.919
Renal organic cation transporter	Non-inhibitor	0.7654
CYP450 2C9 substrate	Non-substrate	0.8329
CYP450 2D6 substrate	Non-substrate	0.7244
CYP450 3A4 substrate	Non-substrate	0.6785
CYP450 1A2 substrate	Non-inhibitor	0.9086
CYP450 2C9 inhibitor	Non-inhibitor	0.8923
CYP450 2D6 inhibitor	Non-inhibitor	0.7561
CYP450 2C19 inhibitor	Non-inhibitor	0.872
CYP450 3A4 inhibitor	Non-inhibitor	0.7651
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.8323
Ames test	Non AMES toxic	0.7955
Carcinogenicity	Non-carcinogens	0.8471
Biodegradation	Not ready biodegradable	0.9782
Rat acute toxicity	2.0121 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9845
hERG inhibition (predictor II)	Non-inhibitor	0.8704

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-01q9-0900000000-eba8c1b56d44c1b807c1
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-03e9-0900000000-c08f5da97f667f13b1db
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-03di-1900000000-972fa1a7c772a975ad9a
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-03di-2900000000-c96720c327f1f9caf8ce
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-03di-5900000000-ba6a44c981963072ddb1
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-06sl-9700000000-010211db22cfecb7a5c2
MS/MS Spectrum - , positive	LC-MS/MS	splash10-03e9-2900000000-3b569e326b02422cd07b

Taxonomy

Description: This compound belongs to the class of organic compounds known as monoalkylamines. These are organic compounds containing an primary aliphatic amine group.
Kingdom: Organic compounds
Super Class: Organic nitrogen compounds
Class: Organonitrogen compounds
Sub Class: Amines
Direct Parent: Monoalkylamines
Alternative Parents: Organopnictogen compounds / Hydrocarbon derivatives
Substituents: Organopnictogen compound / Hydrocarbon derivative / Primary aliphatic amine / Aliphatic homopolycyclic compound
Molecular Framework: Aliphatic homopolycyclic compounds
External Descriptors: Not Available

Targets

Details1. Matrix protein 2

Kind: Protein
Organism: Influenza A virus (strain A/Ann Arbor/6/1960 H2N2)
Pharmacological action: Yes
Actions: Other/unknown

General Function: Ion channel activity
Specific Function: Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytos...
Gene Name: M
Uniprot ID: P21430
Uniprot Name: Matrix protein 2
Molecular Weight: 11165.62 Da

References

Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Jing X, Ma C, Ohigashi Y, Oliveira FA, Jardetzky TS, Pinto LH, Lamb RA: Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10967-72. doi: 10.1073/pnas.0804958105. Epub 2008 Jul 31. [PubMed:18669647]
Melidou A, Kyriazopoulou V, Diza E, Alexiou S, Pierroutsakos Y: Antiviral resistance of influenza A (H3N2) strains isolated in northern Greece between 2004 and 2007. Euro Surveill. 2009 Jan 29;14(4). pii: 19104. [PubMed:19215710]
Chuang GY, Kozakov D, Brenke R, Beglov D, Guarnieri F, Vajda S: Binding hot spots and amantadine orientation in the influenza a virus M2 proton channel. Biophys J. 2009 Nov 18;97(10):2846-53. doi: 10.1016/j.bpj.2009.09.004. [PubMed:19917240]
Intharathep P, Laohpongspaisan C, Rungrotmongkol T, Loisruangsin A, Malaisree M, Decha P, Aruksakunwong O, Chuenpennit K, Kaiyawet N, Sompornpisut P, Pianwanit S, Hannongbua S: How amantadine and rimantadine inhibit proton transport in the M2 protein channel. J Mol Graph Model. 2008 Oct;27(3):342-8. doi: 10.1016/j.jmgm.2008.06.002. Epub 2008 Jun 8. [PubMed:18620883]

Drug created on June 13, 2005 07:24 / Updated on April 03, 2019 09:39

Rimantadine

Identification

Structure for Rimantadine (DB00478)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References