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Identification
Name Rimantadine
Accession Number DB00478 (APRD01219)
Type small molecule
Groups approved
Description

An RNA synthesis inhibitor that is used as an antiviral agent in the prophylaxis and treatment of influenza. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Rimantadine Hydrochloride
Brand names
  • Flumadine
Brand name mixtures Not Available
Categories
  • Antiviral Agents
  • Nucleic Acid Synthesis Inhibitors
CAS number 13392-28-4
Weight Average: 179.3018
Monoisotopic: 179.167399677
Chemical Formula C12H21N
InChI Key InChIKey=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
Plain Text
IUPAC Name
1-(adamantan-1-yl)ethan-1-amine
SMILES
CC(N)C12CC3CC(CC(C3)C1)C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Adamantanes
Substructures
  • Aliphatic and Aryl Amines
  • Adamantanes
  • Cyclooctane and Derivatives
Pharmacology
Indication For the prophylaxis and treatment of illness caused by various strains of influenza A virus in adults.
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.
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
Pharmacoeconomics
Manufacturers
  • Forest laboratories inc
  • Caraco pharmaceutical laboratories ltd
  • Actavis totowa llc
  • Corepharma llc
  • Impax laboratories inc
Packagers
Dosage forms
Form Route Strength
Syrup Oral
Tablet, film coated Oral
Prices
Unit description Cost Unit
Levofloxacin hemihydr 100% powder 42.69 USD g
Levaquin 750 mg leva-pak tablet 27.51 USD tablet
Levaquin 750 mg tablet 27.51 USD tablet
Iquix 1.5% eye drops 15.71 USD ml
Levaquin 500 mg tablet 14.69 USD tablet
Levaquin 250 mg tablet 14.09 USD tablet
Quixin 0.5% eye drops 12.21 USD ml
Rimantadine hcl 100 mg tablet 2.44 USD tablet
Flumadine 100 mg tablet 2.4 USD tablet
Levaquin i.v. 25 mg/ml vial 1.94 USD ml
Levaquin 500 mg/100 ml d5w 0.44 USD ml
Patents Not Available
Properties
State solid
Melting point >300oC
Experimental Properties
Property Value Source
water solubility Hydrochloride salt freely soluble (50 mg/ml at 20°C) PhysProp
logP 3.6 PhysProp
Predicted Properties
Property Value Source
water solubility 9.15e-03 g/l ALOGPS
logP 3.28 ALOGPS
logP 2.22 ChemAxon Molconvert
logS -4.29 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 1 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 26.02 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 54.52 ChemAxon Molconvert
polarizability 21.79 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D08483 Link_out
KEGG Compound C07236 Link_out
PubChem Compound 5071 Link_out
PubChem Substance 46505973 Link_out
ChemSpider 4893 Link_out
BindingDB 50216627 Link_out
Therapeutic Targets Database DAP001087 Link_out
PharmGKB PA451252 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic/rimantadine.htm Link_out
Drugs.com http://www.drugs.com/cdi/rimantadine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Rimantadine Link_out
ATC Codes
  • J05AC02
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (62.4 KB)
MSDS show (62.7 KB)
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. Matrix protein 2

Pharmacological action: yes
Actions: other/unknown

Forms a highly low-pH gated proton-selective channel. When the environmental pH is lower than a threshold, the M2 channel is activated and selectively transports protons across the membrane from the extracellular side to the cytoplasmic side. Crucial for the uncoating process. When the virion is internalized into the endosome, the channel acidifies the virion's interior, promoting the dissociation of matrix protein 1 (M1) from the ribonucleoprotein (RNP) thus allowing the transport of the RNP from the virion into the cell's nucleus. Also plays a role in viral proteins secretory pathway. Elevates the intravesicular pH of normally acidic compartments, such as trans-Golgi network, preventing newly formed hemagglutinin from premature switching to the fusion-active conformation

Organism class: viral
UniProt ID: P21430 Link_out
Gene: M
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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. Epub 2008 Jul 31. Pubmed
  3. 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
  4. 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. Pubmed
  5. 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. Epub 2008 Jun 8. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on December 21, 2010 23:29

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.