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targets (1) enzymes (2)
for drugs
Identification
Name Isosorbide Dinitrate
Accession Number DB00883 (APRD00455)
Type small molecule
Groups approved
Description

A vasodilator used in the treatment of angina pectoris. Its actions are similar to nitroglycerin but with a slower onset of action. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Dianhydrosorbitol 2,5-dinitrate
  • Sorbide nitrate
  • Sorbide, dinitrate
  • Sorbidnitrate
Brand names
  • Cardio 10
  • Cardis
  • Carvanil
  • Carvasin
  • Cedocard
  • Claodical
  • Cornilat
  • Coronex
  • Corosorbide
  • Difutrat
  • Dilatrate
  • Dilatrate-SR
  • Dinitrosorbide
  • Emoper
  • Flindix
  • Harrical
  • IBD 20
  • ISD
  • ISDN
  • Ismotic
  • Iso-Bid
  • Isochron
  • Isoket
  • Isorbid
  • Isordil
  • Isordil Tembids
  • Isostat
  • Isotrate
  • Korodil
  • Lomilan
  • Maycor
  • Myorexon
  • Nitrosorbid
  • Nitrosorbide
  • Nitrosorbon
  • Nosim
  • Resoidan
  • Rifloc Retard
  • Rigedal
  • Sorbangil
  • Sorbide T.D.
  • Sorbidilat
  • Sorbislo
  • Sorbitrate
  • Sorbonit
  • Sorquad
  • Tinidil
  • Titradose
  • Vascardin
  • Vasodilat
  • Vasorbate
  • Xanyl
Brand name mixtures
  • BiDil (isosorbide dinitrate + hydralazine hydrochloride)
Categories
  • Vasodilator Agents
  • Nitrates and Nitrites
  • Nitric Oxide Donors
CAS number 87-33-2
Weight Average: 236.1363
Monoisotopic: 236.028065242
Chemical Formula C6H8N2O8
InChI Key InChIKey=MOYKHGMNXAOIAT-JGWLITMVSA-N
InChI
InChI=1S/C6H8N2O8/c9-7(10)15-3-1-13-6-4(16-8(11)12)2-14-5(3)6/h3-6H,1-2H2/t3-,4+,5-,6-/m1/s1
Plain Text
IUPAC Name
(3R,3aS,6S,6aS)-6-(nitrooxy)-hexahydrofuro[3,2-b]furan-3-yl nitrate
SMILES
[H][C@]12OC[C@H](O[N+]([O-])=O)[C@@]1([H])OC[C@H]2O[N+]([O-])=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Isosorbides
  • Carbohydrates
Substructures
  • Glycerol and Derivatives
  • Oxoazaniums
  • Ethers
  • Esters
  • Isosorbides
  • Heterocyclic compounds
  • Furans
  • Nitrates
  • Carbohydrates
Pharmacology
Indication For the prevention of angina pectoris due to coronary artery disease.
Pharmacodynamics Isosorbide Dinitrate is a moderate to long acting oral organic nitrate used for the relief and prophylactic management of angina pectoris. It relaxes the vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter. Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end- diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure.
Mechanism of action Similar to other nitrites and organic nitrates, isosorbide dinitrate is converted to nitric oxide (NO), an active intermediate compound which activates the enzyme guanylate cyclase (atrial natriuretic peptide receptor A). This stimulates the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP) which then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells, eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber. The subsequent release of calcium ions results in the relaxation of the smooth muscle cells and vasodilation.
Absorption Absorption of isosorbide dinitrate after oral dosing is nearly complete, but bioavailability is highly variable (10% to 90%), with extensive first-pass metabolism in the liver. The average bioavailability of isosorbide dinitrate is about 25%.
Volume of distribution
  • 2 to 4 L/kg
Protein binding Very low
Metabolism

Hepatic
Route of elimination Not Available
Half life 1 hour
Clearance Not Available
Toxicity Symptoms of overdose include reduced cardiac output and hypotension.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Alcon laboratories inc
  • Schwarz pharma inc
  • Wyeth ayerst laboratories
  • Astrazeneca pharmaceuticals lp
  • Caraco pharmaceutical laboratories ltd
  • Corepharma llc
  • Biovail laboratories inc
  • Mutual pharmaceutical co inc
  • Par pharmaceutical inc
  • Sandoz inc
  • Superpharm corp
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • West ward inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Tablet Sublingual
Tablet, extended release Oral
Prices
Unit description Cost Unit
Isordil Titradose 40 mg tablet 1.7 USD tablet
Isordil 40 mg tablet 1.58 USD tablet
Dilatrate-sr 40 mg capsule 1.48 USD capsule
Isochron 40 mg tablet sa 1.07 USD tablet
Isosorbide Dinitrate CR 40 mg Controlled Release Tabs 0.88 USD tab
Isosorbide Mononitrate 20 mg tablet 0.78 USD tablet
Isosorbide Mononitrate 10 mg tablet 0.74 USD tablet
Isordil Titradose 5 mg tablet 0.68 USD tablet
Isordil 5 mg tablet 0.65 USD tablet
Isosorbide dn 30 mg tablet 0.53 USD tablet
Isordil 10 mg tablet 0.5 USD tablet
Isosorbide Dinitrate 30 mg tablet 0.5 USD tablet
Cedocard-Sr 20 mg Sustained-Release Tablet 0.44 USD tablet
Isosorbide Dinitrate 10 mg tablet 0.43 USD tablet
Isosorbide Dinitrate 20 mg tablet 0.43 USD tablet
Isosorbide Dinitrate 2.5 mg Sublingual Tabs 0.39 USD tab
Isosorbide Dinitrate 5 mg Sublingual Tabs 0.21 USD tab
Isosorbide dn 2.5 mg tablet sl 0.21 USD tablet
Isosorbide dn 5 mg tablet sl 0.21 USD tablet
Isosorbide dn 20 mg tablet 0.2 USD tablet
Isosorbide Dinitrate 5 mg tablet 0.17 USD tablet
Isosorbide dn 10 mg tablet 0.17 USD tablet
Isosorbide dn 5 mg tablet 0.17 USD tablet
Apo-Isdn 30 mg Tablet 0.09 USD tablet
Apo-Isdn 5 mg Sublingual Tablet 0.07 USD tablet
Apo-Isdn 10 mg Tablet 0.04 USD tablet
Patents Not Available
Properties
State solid
Melting point 70
Experimental Properties
Property Value Source
water solubility 0.55 mg/mL [YALKOWSKY,SH & DANNENFELSER,RM (1992)] PhysProp
logP 1.31 [HANSCH,C ET AL. (1995)] PhysProp
logS -2.63 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 9.38e-01 g/l ALOGPS
logP 0.87 ALOGPS
logP 0.44 ChemAxon Molconvert
logS -2.40 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 8 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 128.56 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 44.77 ChemAxon Molconvert
polarizability 18.07 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00516 Link_out
KEGG Compound C07456 Link_out
PubChem Compound 6883 Link_out
PubChem Substance 46506412 Link_out
ChemSpider 6619 Link_out
ChEBI 6061 Link_out
ChEMBL 6061 Link_out
Therapeutic Targets Database DAP001057 Link_out
PharmGKB PA450125 Link_out
Drug Product Database 670944 Link_out
RxList http://www.rxlist.com/cgi/generic2/isodinit.htm Link_out
Drugs.com http://www.drugs.com/cdi/isosorbide-dinitrate.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/iso1212.shtml Link_out
ATC Codes
  • C01DA08
  • D03AX08
AHFS Codes
  • 24:12.08
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals. Absorption is faster on an empty stomach.
Targets

1. Atrial natriuretic peptide receptor A

Pharmacological action: yes
Actions: agonist

Receptor for atrial natriuretic peptide. Has guanylate cyclase activity on binding of ANF

Organism class: human
UniProt ID: P16066 Link_out
Gene: NPR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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
  3. Villarroya M, Lopez MG, de Pascual R, Garcia AG: Preclinical profile of PF9404C, a nitric oxide donor with beta receptor blocking properties. Cardiovasc Drug Rev. 2005 Summer;23(2):149-60. Pubmed
  4. Takabuchi S, Hirota K, Nishi K, Oda S, Oda T, Shingu K, Takabayashi A, Adachi T, Semenza GL, Fukuda K: The inhibitory effect of sodium nitroprusside on HIF-1 activation is not dependent on nitric oxide-soluble guanylyl cyclase pathway. Biochem Biophys Res Commun. 2004 Nov 5;324(1):417-23. Pubmed
  5. Beauregard C, Brandt PC, Chiou GC: Nitric oxide and cyclic GMP-mediated protein secretion from cultured lacrimal gland acinar cells. J Ocul Pharmacol Ther. 2002 Oct;18(5):429-43. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2E1

Actions: inhibitor

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on May 24, 2011 13:29

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.