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 pectoris 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
Synonyms
  • IS 5-MN
  • IS-5-MN
  • IS-5MN
  • ISMN
  • Iso-5-mononitrate
  • Isosorbide 5-mononitrate
  • Isosorbide 5-nitrate
  • Isosorbide-5-mononitrate
  • isosorbidi mononitras
  • mononitrate d'isosorbide
  • mononitrato de isosorbida
  • Monosorbitrate
External IDs
AHR-4698 / BM 22.145 / BM-22.145 / BM-22145
Active Moieties
NameKindUNIICASInChI Key
IsosorbideunknownWXR179L51S652-67-5KLDXJTOLSGUMSJ-JGWLITMVSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ImdurTablet60 mg/1OralSchering Corporation2003-09-012006-10-31Us
ImdurTablet30 mg/1OralSchering Corporation2003-09-012006-10-31Us
ImdurTablet120 mg/1OralSchering Corporation2003-09-012006-11-30Us
Imdur - Extended Release Tablets 60 mgTablet, extended release60 mgOralAstra Zeneca1994-12-31Not applicableCanada
IsmnTablet, extended release60 mgOralSivem Pharmaceuticals Ulc2015-10-082017-06-27Canada
IsmoTablet, film coated20 mg/1OralReddy Pharmaceuticals, LLC2007-03-31Not applicableUs
Ismo Tab 20mgTablet20 mgOralWyeth Ayerst Canada Inc.1994-12-312002-06-10Canada
MonoketTablet20 mg/1OralUcb Inc1993-06-302012-07-30Us
MonoketTablet20 mg/1OralKremers Urban1993-06-30Not applicableUs
MonoketTablet10 mg/1OralUcb Inc1993-06-302012-07-11Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-ismnTablet, extended release60 mgOralApotex Corporation2006-03-03Not applicableCanada
Dom-ismnTablet, extended release60 mgOralDominion PharmacalNot applicableNot applicableCanada
ImdurTablet, extended release120 mg/1OralSchering Corporation2006-01-052017-04-06Us
ImdurTablet, extended release30 mg/1OralPhysicians Total Care, Inc.2009-12-022012-06-30Us
ImdurTablet, extended release60 mg/1OralSchering Corporation2006-01-052017-04-06Us
ImdurTablet, extended release60 mg/1OralPhysicians Total Care, Inc.1997-01-032012-06-30Us
ImdurTablet, extended release30 mg/1OralSchering Corporation2006-01-052017-04-06Us
Isorsorbide MononitrateTablet, film coated, extended release60 mg/1OralActavis Pharma Company2005-05-042006-07-30Us
Isorsorbide MononitrateTablet, film coated, extended release30 mg/1OralActavis Pharma Company2005-05-042006-07-30Us
IsosorbideTablet, film coated, extended release120 mg/1OralMed Health Pharma LLC.2011-03-252012-04-15Us
International/Other Brands
Chemydur / Corangin / Dilatrate / Duride / Elantan / Etimonis / Imodur / Imtrate / Ismexin / Ismo / Ismox / Isomon / Isomonit / Isonorm / Medocor / Monicor / Monit / Mono Corax / Mono Mack / Monocedocard / Monoclair / Monocord / Monodur Durules / Monolong / Monomax / Mononit / Monopront / Monosorb / Monosordil / Monotrate / Nitramin / Olicard / Olicardin / Orasorbil / Pertil / Plodin / Promocard / Sigacora / Solotrate / Sorbimon / Turimonit / Uniket / Vasdilat
Categories
UNII
LX1OH63030
CAS number
16051-77-7
Weight
Average: 191.1388
Monoisotopic: 191.042987025
Chemical Formula
C6H9NO6
InChI Key
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
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

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.

Associated Conditions
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.

TargetActionsOrganism
AGuanylate cyclase soluble subunit alpha-2
inducer
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Isosorbide Mononitrate.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Isosorbide Mononitrate.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Isosorbide Mononitrate.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Isosorbide Mononitrate.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Isosorbide Mononitrate.
6-Deoxyerythronolide BThe metabolism of Isosorbide Mononitrate can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Isosorbide Mononitrate.
AbacavirIsosorbide Mononitrate may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Isosorbide Mononitrate.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Isosorbide Mononitrate.
Food Interactions
  • Take without regard to meals.

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015155
KEGG Drug
D00630
KEGG Compound
C07714
PubChem Compound
27661
PubChem Substance
46506594
ChemSpider
25736
ChEBI
6062
ChEMBL
CHEMBL1311
Therapeutic Targets Database
DAP001058
PharmGKB
PA450126
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
ATC Codes
C01DA14 — Isosorbide mononitrate
AHFS Codes
  • 24:12.08 — Nitrates and Nitrites
FDA label
Download (217 KB)
MSDS
Download (66.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedDiagnosticHigh Blood Pressure (Hypertension)1
1CompletedTreatmentBioequivalence1
1CompletedTreatmentCoronary Artery Disease1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentHigh Blood Pressure (Hypertension)2
1Not Yet RecruitingTreatmentAnal Fissures1
2CompletedPreventionCerebral Small Vessels Disease / Cognitive Impairments / Strokes1
2CompletedTreatmentHeart Failure, Unspecified / Preserved Ejection Fraction1
2RecruitingOtherRenal Insufficiency,Chronic1
2RecruitingTreatmentCervical Ripening1
2RecruitingTreatmentMissed Abortion1
2, 3CompletedTreatmentIsolated (Idiopathic) Oligohydramnios1
2, 3RecruitingPreventionCerebral Small Vessels Disease / Stroke, Lacunar1
3RecruitingSupportive CareInduction of Labor Affected Fetus / Newborn1
3RecruitingSupportive CareInduction of Labor Affected Fetus / Newborn / Rupture of Membranes Prior to Onset of Labor1
3Unknown StatusTreatmentStable Angina (SA)1
4CompletedPreventionHemorrhage, Gastrointestinal / Liver Cirrhosis / Portal Hypertension1
4CompletedPreventionVariceal Rebleeding1
4CompletedTreatmentMyocardial Ischemia / Quality of Life / Stable Angina (SA)1
4CompletedTreatmentSecond Trimester Abortions1
Not AvailableCompletedTreatmentMigraines1
Not AvailableCompletedTreatmentType 2 Diabetes Mellitus1
Not AvailableNot Yet RecruitingTreatmentIUD Insertion Complication1
Not AvailableRecruitingPreventionPreeclampsia / Premature Labour1

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
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • Alvogen Inc.
  • Apothecon
  • A-S Medication Solutions LLC
  • AstraZeneca Inc.
  • Atlantic Biologicals Corporation
  • Bryant Ranch Prepack
  • Cardinal Health
  • Comprehensive Consultant Services Inc.
  • Dexcel Ltd.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Elan Pharmaceuticals Inc.
  • Ethex Corp.
  • Heartland Repack Services LLC
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Mckesson Corp.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Neuman Distributors Inc.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Prepak Systems Inc.
  • Promius Pharma
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Schering Corp.
  • Schwarz Pharma Inc.
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
  • Vangard Labs Inc.
  • West-Ward Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral120 mg/1
TabletOral30 mg/1
TabletOral60 mg/1
Tablet, extended releaseOral60 mg
Tablet, film coatedOral20 mg/1
TabletOral20 mg
TabletOral10 mg/1
TabletOral20 mg/1
Tablet, coatedOral20 mg/1
Tablet, extended releaseOral120 mg/1
Tablet, extended releaseOral30 mg/1
Tablet, extended releaseOral60 mg/1
Tablet, film coated, extended releaseOral120 mg/1
Tablet, film coated, extended releaseOral30 mg/1
Tablet, film coated, extended releaseOral60 mg/1
Prices
Unit descriptionCostUnit
Imdur er 120 mg tablet4.19USD tablet
Imdur 120 mg 24 Hour tablet3.15USD tablet
Imdur 60 mg 24 Hour tablet3.11USD tablet
Imdur er 60 mg tablet2.99USD tablet
Imdur 30 mg 24 Hour tablet2.87USD tablet
Imdur er 30 mg tablet2.85USD tablet
Monoket 20 mg tablet2.65USD tablet
Ismo 20 mg tablet2.1USD tablet
Monoket 10 mg tablet1.75USD tablet
Isosorbide Mononitrate CR 60 mg 24 Hour tablet1.48USD tablet
Isosorbide Mononitrate CR 30 mg 24 Hour tablet1.16USD tablet
Isosorbide Mononitrate 20 mg tablet0.78USD tablet
Isosorbide Mononitrate 10 mg tablet0.74USD tablet
Imdur 60 mg Extended-Release Tablet0.74USD tablet
Isosorbide mn 20 mg tablet0.72USD tablet
Isosorbide mn 10 mg tablet0.71USD tablet
Apo-Ismn 60 mg Extended-Release Tablet0.42USD tablet
Pms-Ismn 60 mg Extended-Release Tablet0.42USD tablet
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)88-91 °CNot Available
water solubility1.07E+005 mg/LNot Available
logP-0.15SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility57.0 mg/mLALOGPS
logP-0.74ALOGPS
logP-0.48ChemAxon
logS-0.53ALOGPS
pKa (Strongest Acidic)13.34ChemAxon
pKa (Strongest Basic)-3.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area93.74 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity38.08 m3·mol-1ChemAxon
Polarizability15.85 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9156
Blood Brain Barrier+0.9355
Caco-2 permeable-0.579
P-glycoprotein substrateNon-substrate0.7621
P-glycoprotein inhibitor INon-inhibitor0.7159
P-glycoprotein inhibitor IINon-inhibitor0.9116
Renal organic cation transporterNon-inhibitor0.8563
CYP450 2C9 substrateNon-substrate0.8674
CYP450 2D6 substrateNon-substrate0.8613
CYP450 3A4 substrateSubstrate0.5357
CYP450 1A2 substrateNon-inhibitor0.8532
CYP450 2C9 inhibitorNon-inhibitor0.8769
CYP450 2D6 inhibitorNon-inhibitor0.9106
CYP450 2C19 inhibitorNon-inhibitor0.8469
CYP450 3A4 inhibitorNon-inhibitor0.9471
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9596
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.7696
BiodegradationReady biodegradable0.8359
Rat acute toxicity2.0753 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5741
hERG inhibition (predictor II)Non-inhibitor0.9304
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as isosorbides. These are organic polycyclic compounds containing an isosorbide(1,4-Dianhydrosorbitol) moiety, which consists of two -oxolan-3-ol rings.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Furofurans
Sub Class
Isosorbides
Direct Parent
Isosorbides
Alternative Parents
Tetrahydrofurans / Alkyl nitrates / Secondary alcohols / Organic nitro compounds / Organic nitric acids and derivatives / Oxacyclic compounds / Dialkyl ethers / Organic zwitterions / Organic oxides / Organic nitrogen compounds
show 1 more
Substituents
Isosorbide / Organic nitrate / Tetrahydrofuran / Alkyl nitrate / Organic nitric acid or derivatives / Secondary alcohol / Organic nitro compound / Dialkyl ether / Ether / Oxacycle
show 10 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
nitrate ester, glucitol derivative (CHEBI:6062)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inducer
General Function
Heme binding
Specific Function
Has guanylyl cyclase on binding to the beta-1 subunit.Isoform 2 acts as a negative regulator of guanylyl cyclase activity as it forms non-functional heterodimers with the beta subunits.
Gene Name
GUCY1A2
Uniprot ID
P33402
Uniprot Name
Guanylate cyclase soluble subunit alpha-2
Molecular Weight
81749.185 Da
References
  1. Moncada S, Palmer RM, Higgs EA: Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109-42. [PubMed:1852778]
  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;113(3):563-75. doi: 10.1111/j.1471-4159.2010.06606.x. Epub 2010 Jan 20. [PubMed:20089135]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on November 20, 2018 13:19