Banner
targets (1) enzymes (1)
for drugs
Identification
Name Isosorbide Mononitrate
Accession Number DB01020 (APRD00528)
Type small molecule
Groups approved
Description

Isosorbide mononitrate is a drug used principally in the treatment of angina pectoris1 and acts by dilating the blood vessels so as to reduce the blood pressure. It is sold by AstraZeneca under the trade name Imdur.

Isosorbide mononitrate is used to for the the prophylactic treatment of angina pectoris; that is, it is taken in order to prevent or at least reduce the occurrence of angina. Research on Isosorbide mononitrate as a cervical ripener to reduce time at hospital to birth is supportive.

Isosorbide mononitrate is an active metabolite of isosorbide dinitrate and exerts qualitatively similar effects. Isosorbide mononitrate reduces the workload of the heart by producing venous and arterial dilation. By reducing the end diastolic pressure and volume, isosorbide mononitrate lowers intramural pressure, hence leading to an improvement in the subendocardial blood flow. The net effect when administering isosorbide mononitrate is therefore a reduced workload for the heart and an improvement in the oxygen supply/demand balance of the myocardium.

The adverse reactions which follow have been reported in studies with isosorbide mononitrate:
Very common. Headache predominates (up to 30%) necessitating withdrawal of 2 to 3 % of patients, but the incidence reduces rapidly as treatment continues .
Common. Tiredness, sleep disturbances (6%) and gastrointestinal disturbances (6%) have been reported during clinical trials with isosorbide mononitrate modified release tablets, but at a frequency no greater than for placebo. Hypotension (4 to 5%), poor appetite (2.5%), nausea (1%).
Adverse effects associated with the clinical use of the drug are as expected with all nitrate preparations. They occur mainly in the early stages of treatment.
Hypotension (4%) with symptoms such as dizziness and nausea (1%) have been reported. These symptoms generally disappear during long-term treatment.
Other reactions that have been reported with isosorbide mononitrate modified release tablets include tachycardia, vomiting, diarrhoea, vertigo and heartburn
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • IHD
  • ISMN
  • Isosorbidi Mononitras [Latin]
  • Mononitrate d'Isosorbide [French]
  • Mononitrato de Isosorbida [Spanish]
  • Monosorbitrate
Brand names
  • Conpin
  • Conpin Retardkaps
  • Corangin
  • Corangin Sr
  • Duride
  • Edistol
  • Elantan
  • Elantan Long
  • Elantan Retard
  • Epicordin
  • Etimonis
  • Fem-Mono
  • Imazin
  • Imdur
  • Imdur 60
  • Imdur Durules
  • Imodur
  • Imtrate
  • IS 5MN
  • Ismexin
  • Ismn Abz
  • ISMN AL
  • Ismn Apogepha
  • Ismn Atid
  • Ismn Basics
  • Ismn Heumann
  • Ismn Hexal
  • Ismn Lannacher
  • Ismn Stada
  • Ismo
  • Ismo-20
  • Ismox
  • Isomon
  • Isomonat
  • Isomonit
  • Isopen-20
  • Iturol
  • Medocor
  • Monicor
  • Monis
  • Monisid
  • Monit
  • Monit 20
  • Monizid
  • Mono Corax
  • Mono Corax Retard
  • Mono Mack
  • Mono-Mack
  • Mono-Sanorania
  • Monocedocard
  • Monoclair
  • Monocord 20
  • Monocord 40
  • Monocord 50 Sr
  • Monodur Durules
  • Monoket
  • Monoket Od
  • Monoket Retard
  • Monolong
  • Monolong 40
  • Monolong 60
  • Mononit
  • Mononit 20
  • Mononit 40
  • Mononit Retard 50
  • Monopront
  • Monosigma
  • Monosorb
  • Monosordil
  • Monotrate
  • Multitab
  • Nitex
  • Nitramin
  • Olicard
  • Olicardin
  • Orasorbil
  • Pentacard
  • Pentacard 20
  • Percorina
  • Pertil
  • Plodin
  • Promocard
  • Sigacora
  • Sorbimon
  • Titarane
  • Turimonit
  • Uniket
  • Vasdilat
  • Vasotrate
Brand name mixtures Not Available
Categories
  • Vasodilator Agents
  • Nitrates and Nitrites
  • Nitric Oxide Donors
CAS number 16051-77-7
Weight Average: 191.1388
Monoisotopic: 191.042987025
Chemical Formula C6H9NO6
InChI Key InChIKey=YWXYYJSYQOXTPL-SLPGGIOYSA-N
InChI
InChI=1S/C6H9NO6/c8-3-1-11-6-4(13-7(9)10)2-12-5(3)6/h3-6,8H,1-2H2/t3-,4+,5+,6+/m0/s1
Plain Text
IUPAC Name
(3R,3aS,6S,6aR)-6-hydroxy-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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Isosorbides
  • Carbohydrates
Substructures
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Oxoazaniums
  • Ethers
  • Esters
  • Isosorbides
  • Heterocyclic compounds
  • Furans
  • Nitrates
  • Alcohols and Polyols
  • Carbohydrates
Pharmacology
Indication For the prevention of angina pectoris due to coronary artery disease and the treatment of acute and chronic angina pectoris, hypertension, and myocardial infarction.
Pharmacodynamics Isosorbide-5-mononitrate, the long-acting metabolite of isosorbide dinitrate, is used as a vasodilatory agent in the management of angina pectoris. By dilating the vessels, it lowers the blood pressure and reduces the left ventricular preload and afterload, therefore, leads to a reduction of myocardial oxygen requirement.
Mechanism of action Similar to other nitrites and organic nitrates, Isosorbide Mononitrate 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 100%
Volume of distribution
  • 0.6 to 0.7 L/kg
Protein binding 5%
Metabolism

Hepatic
Route of elimination Isosorbide mononitrate is primarily metabolized by the liver, but unlike oral isosorbide dinitrate, it is not subject to first-pass metabolism. Isosorbide mononitrate is cleared by denitration to isosorbide and glucuronidation as the mononitrate, with 96% of the administered dose excreted in the urine within 5 days and only about 1% eliminated in the feces. At least six different compounds have been detected in urine, with about 2% of the dose excreted as the unchanged drug and at least five metabolites.
Half life 5 hours
Clearance
  • 120–122 mL/min [Single dose of 60 mg PO]
  • 151–187 mL/min [Single dose of extended-release tablet 60 mg PO]
  • 132-151 mL/min [Multiple doses of extended release tablet 60 mg PO]
  • 119-140 mL/min [Multiple doses of extended release tablet 120 mg PO]
Toxicity Symptoms of overdose include vasodilatation, venous pooling, reduced cardiac output, and hypotension. There are no data suggesting what dose of isosorbide mononitrate is likely to be life-threatening in humans. In rats and mice, there is significant lethality at doses of 2000 mg/kg and 3000 mg/kg, respectively.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Schering plough corp
  • Actavis elizabeth llc
  • Brightstone pharma inc
  • Dexcel ltd
  • Elan pharmaceutical research corp
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Kremers urban co
  • Kv pharmaceutical co
  • Vintage pharmaceuticals inc
  • West ward pharmaceutical corp
  • Promius pharma llc
  • Teva pharmaceuticals usa inc
  • Schwarz gmbh
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Imdur er 120 mg tablet 4.19 USD tablet
Imdur 120 mg 24 Hour tablet 3.15 USD tablet
Imdur 60 mg 24 Hour tablet 3.11 USD tablet
Imdur er 60 mg tablet 2.99 USD tablet
Imdur 30 mg 24 Hour tablet 2.87 USD tablet
Imdur er 30 mg tablet 2.85 USD tablet
Monoket 20 mg tablet 2.65 USD tablet
Ismo 20 mg tablet 2.1 USD tablet
Monoket 10 mg tablet 1.75 USD tablet
Isosorbide Mononitrate CR 60 mg 24 Hour tablet 1.48 USD tablet
Isosorbide Mononitrate CR 30 mg 24 Hour tablet 1.16 USD tablet
Isosorbide Mononitrate 20 mg tablet 0.78 USD tablet
Isosorbide Mononitrate 10 mg tablet 0.74 USD tablet
Imdur 60 mg Extended-Release Tablet 0.74 USD tablet
Isosorbide mn 20 mg tablet 0.72 USD tablet
Isosorbide mn 10 mg tablet 0.71 USD tablet
Apo-Ismn 60 mg Extended-Release Tablet 0.42 USD tablet
Pms-Ismn 60 mg Extended-Release Tablet 0.42 USD tablet
Patents Not Available
Properties
State solid
Melting point 88-91oC
Experimental Properties
Property Value Source
water solubility 1.07E+005 mg/L PhysProp
logP -0.9 PhysProp
Predicted Properties
Property Value Source
water solubility 5.70e+01 g/l ALOGPS
logP -0.74 ALOGPS
logP -0.48 ChemAxon Molconvert
logS -0.53 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 93.74 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 38.08 ChemAxon Molconvert
polarizability 15.85 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00630 Link_out
KEGG Compound C07714 Link_out
PubChem Compound 27661 Link_out
PubChem Substance 46506594 Link_out
ChemSpider 25736 Link_out
ChEBI 6062 Link_out
ChEMBL 6062 Link_out
Therapeutic Targets Database DAP001058 Link_out
Drug Product Database 2126559 Link_out
RxList http://www.rxlist.com/cgi/generic/isomono2.htm Link_out
Drugs.com http://www.drugs.com/isosorbide_mononitrate.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Isosorbide_mononitrate Link_out
ATC Codes
  • C01DA14
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (217.4 KB)
MSDS show (66.5 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
Targets

1. Guanylate cyclase soluble subunit alpha-2

Pharmacological action: yes
Actions: inducer

Has guanylyl cyclase on binding to the beta-1 subunit. The alternatively spliced isoform alpha-2-I acts as a negative regulator of guanylyl cyclase activity as it forms non-functional heterodimers with the beta subunits

Organism class: human
UniProt ID: P33402 Link_out
Gene: GUCY1A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Moncada S, Palmer RM, Higgs EA: Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109-42. Pubmed
  2. Mancuso C, Navarra P, Preziosi P: Roles of nitric oxide, carbon monoxide, and hydrogen sulfide in the regulation of the hypothalamic-pituitary-adrenal axis. J Neurochem. 2010 May 1;113(3):563-75. Epub 2010 Jan 20. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:08

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.