Rimantadine

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. [PubChem]

Structure
Thumb
Synonyms
  • Rimantadin
  • Rimantadine
Product Ingredients
IngredientUNIICASInChI Key
Rimantadine HydrochlorideJEI07OOS8Y1501-84-4OZBDFBJXRJWNAV-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FlumadineTablet100 mg/1OralFOREST PHARMACEUTICALS, INC.2007-07-10Not applicableUs
FlumadineTablet100 mg/1OralCaraco Pharma, Inc.2009-09-22Not applicableUs
FlumadineSyrup50 mg/5mLOralFOREST PHARMACEUTICALS, INC.2007-07-10Not applicableUs
FlumadineTablet100 mg/1OralPhysicians Total Care, Inc.2009-09-222010-06-30Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Rimantadine HydrochlorideTablet, film coated100 mg/1OralH.J. Harkins Company2005-04-01Not applicableUs
Rimantadine HydrochlorideTablet, film coated100 mg/1OralImpax Generics2005-04-01Not applicableUs
Rimantadine HydrochlorideTablet, film coated100 mg/1OralStat Rx USA2005-04-01Not applicableUs
Rimantadine HydrochlorideTablet, film coated100 mg/1OralCarilion Materials Management2005-04-01Not applicableUs
Rimantadine HydrochlorideTablet, film coated100 mg/1OralSandoz2001-11-022012-03-31Us
Rimantadine HydrochlorideTablet, film coated100 mg/1Oralbryant ranch prepack2005-04-01Not applicableUs
Rimantadine HydrochlorideTablet, film coated100 mg/1OralA-S Medication Solutions2005-04-01Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
RimantalistRimantadine Hydrochloride (100 mg/1) + L-Arginine (60 mg/1)KitPhysician Therapeutics Llc2011-07-07Not applicableUs
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
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.

TargetActionsOrganism
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
DrugInteraction
Influenza a virus a/california/7/2009 (h1n1) live (attenuated) antigenThe 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) antigenThe 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
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
2CompletedNot AvailableHepatitis C Viral Infection1

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
FormRouteStrength
SyrupOral50 mg/5mL
TabletOral100 mg/1
Tablet, film coatedOral100 mg/1
Kit
Prices
Unit descriptionCostUnit
Levofloxacin hemihydr 100% powder42.69USD g
Levaquin 750 mg leva-pak tablet27.51USD tablet
Levaquin 750 mg tablet27.51USD tablet
Iquix 1.5% eye drops15.71USD ml
Levaquin 500 mg tablet14.69USD tablet
Levaquin 250 mg tablet14.09USD tablet
Quixin 0.5% eye drops12.21USD ml
Rimantadine hcl 100 mg tablet2.44USD tablet
Flumadine 100 mg tablet2.4USD tablet
Levaquin i.v. 25 mg/ml vial1.94USD ml
Levaquin 500 mg/100 ml d5w0.44USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)>300 °CNot Available
water solubilityHydrochloride salt freely soluble (50 mg/ml at 20 °C)Not Available
logP3.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00915 mg/mLALOGPS
logP3.28ALOGPS
logP2.22ChemAxon
logS-4.3ALOGPS
pKa (Strongest Basic)10.14ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area26.02 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity54.52 m3·mol-1ChemAxon
Polarizability21.79 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9798
Caco-2 permeable+0.6348
P-glycoprotein substrateNon-substrate0.6811
P-glycoprotein inhibitor INon-inhibitor0.8751
P-glycoprotein inhibitor IINon-inhibitor0.919
Renal organic cation transporterNon-inhibitor0.7654
CYP450 2C9 substrateNon-substrate0.8329
CYP450 2D6 substrateNon-substrate0.7244
CYP450 3A4 substrateNon-substrate0.6785
CYP450 1A2 substrateNon-inhibitor0.9086
CYP450 2C9 inhibitorNon-inhibitor0.8923
CYP450 2D6 inhibitorNon-inhibitor0.7561
CYP450 2C19 inhibitorNon-inhibitor0.872
CYP450 3A4 inhibitorNon-inhibitor0.7651
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8323
Ames testNon AMES toxic0.7955
CarcinogenicityNon-carcinogens0.8471
BiodegradationNot ready biodegradable0.9782
Rat acute toxicity2.0121 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9845
hERG inhibition (predictor II)Non-inhibitor0.8704
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-01q9-0900000000-eba8c1b56d44c1b807c1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03e9-0900000000-c08f5da97f667f13b1db
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-1900000000-972fa1a7c772a975ad9a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-2900000000-c96720c327f1f9caf8ce
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-5900000000-ba6a44c981963072ddb1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-06sl-9700000000-010211db22cfecb7a5c2
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03e9-2900000000-3b569e326b02422cd07b

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

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
  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:17016423]
  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. doi: 10.1073/pnas.0804958105. Epub 2008 Jul 31. [PubMed:18669647]
  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:19215710]
  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. doi: 10.1016/j.bpj.2009.09.004. [PubMed:19917240]
  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. doi: 10.1016/j.jmgm.2008.06.002. Epub 2008 Jun 8. [PubMed:18620883]

Drug created on June 13, 2005 07:24 / Updated on December 14, 2018 16:24