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Showing drug card for Isosorbide Dinitrate (DB00883)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:07:59
Primary Accession Number DB00883
Secondary Accession Number
  • APRD00455
Name Isosorbide Dinitrate
Drug Type
  • Approved
  • Small Molecule
Description A vasodilator used in the treatment of angina pectoris. Its actions are similar to nitroglycerin but with a slower onset of action. [PubChem]
Synonyms
  1. Dianhydrosorbitol 2,5-dinitrate
  2. Sorbide nitrate
  3. Sorbide, dinitrate
  4. Sorbidnitrate
Brand Names
  1. Cardio 10
  2. Cardis
  3. Carvanil
  4. Carvasin
  5. Cedocard
  6. Claodical
  7. Cornilat
  8. Coronex
  9. Corosorbide
  10. Difutrat
  11. Dilatrate
  12. Dilatrate-SR
  13. Dinitrosorbide
  14. Emoper
  15. Flindix
  16. Harrical
  17. IBD 20
  18. ISD
  19. ISDN
  20. Ismotic
  21. Iso-Bid
  22. Isochron
  23. Isoket
  24. Isorbid
  25. Isordil
  26. Isordil Tembids
  27. Isostat
  28. Isotrate
  29. Korodil
  30. Lomilan
  31. Maycor
  32. Myorexon
  33. Nitrosorbid
  34. Nitrosorbide
  35. Nitrosorbon
  36. Nosim
  37. Resoidan
  38. Rifloc Retard
  39. Rigedal
  40. Sorbangil
  41. Sorbide T.D.
  42. Sorbidilat
  43. Sorbislo
  44. Sorbitrate
  45. Sorbonit
  46. Sorquad
  47. Tinidil
  48. Titradose
  49. Vascardin
  50. Vasodilat
  51. Vasorbate
  52. Xanyl
Brand Mixtures
  1. BiDil (isosorbide dinitrate + hydralazine hydrochloride)
Chemical IUPAC Name [(3S,3aS,6R,6aS)-6-nitrooxy-2,3,3a,5,6,6a-hexahydrofuro[2,3-d]furan-3-yl] nitrate
Chemical Formula C6H8N2O8
Chemical Structure Structure
CAS Registry Number 87-33-2
InChI Identifier InChI=1/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
InChI Key MOYKHGMNXAOIAT-JGWLITMVBQ
KEGG Drug D00516 Link Image
KEGG Compound C07456 Link Image
PubChem Compound 6883 Link Image
PubChem Substance 7979661 Link Image
ChEBI ID Not Available
PharmGKB ID PA450125 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 00670944 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/isodinit.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/iso1212.shtml Link Image
Wikipedia Link Not Available
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Goldberg, Acta physiol. Scand.15, 173(1948)
Average Molecular Weight 236.1363
Monoisotopic Molecular Weight 236.0281
State Solid
Melting Point 70 oC
Experimental Water Solubility 1.089 mg/mL Source: PhysProp
Predicted Water Solubility 9.38e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity
Predicted LogP 0.87 Calculated using ALOGPS
Experimental LogS -2.63 [ADME Research, USCD]
Predicted LogS -2.40 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@H](CO[C@H]12)O[N+]([O-])=O
Canonical SMILES [O-][N+](=O)OC1COC2C(COC12)O[N+]([O-])=O
Drug Category
  • Nitrates and Nitrites
  • Nitric Oxide Donors
  • Vasodilator Agents
ATC Codes
AHFS Codes
  • 24:12.08
Indication For the prevention of angina pectoris due to coronary artery disease.
Pharmacology 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%.
Toxicity Symptoms of overdose include reduced cardiac output and hypotension.
Protein Binding Very low
Biotransformation Hepatic
Half Life 1 hour
Dosage Forms
Form Route
Tablet Oral
Tablet Sublingual
Tablet, extended release Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Dihydroergotamine Possible antagonism of action
Dihydroergotoxine Possible antagonism of action
Ergonovine Possible antagonism of action
Ergotamine Possible antagonism of action
Methylergonovine Possible antagonism of action
Methysergide Possible antagonism of action
Sildenafil Possible significant hypotension with this combination
Tadalafil Possible significant hypotension with this combination
Vardenafil Possible significant hypotension with this combination
Food Interactions
  • Take without regard to meals. Absorption is faster on an empty stomach.
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. RxList Link Image
  3. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
Targets
  1. Atrial natriuretic peptide receptor A
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Drug Target 1 [top]
Target 1 ID 613
Target 1 Name Atrial natriuretic peptide receptor A
Target 1 Synonyms
  1. ANP-A
  2. ANPRA
  3. Atrial natriuretic peptide A-type receptor
  4. Atrial natriuretic peptide receptor A precursor
  5. EC 4.6.1.2
  6. GC-A
  7. Guanylate cyclase
  8. NPR-A
Target 1 Gene Name NPR1
Target 1 Protein Sequence >Atrial natriuretic peptide receptor A precursor 
MPGPRRPAGSRLRLLLLLLLPPLLLLLRGSHAGNLTVAVVLPLANTSYPWSWARVGPAVE
LALAQVKARPDLLPGWTVRTVLGSSENALGVCSDTAAPLAAVDLKWEHNPAVFLGPGCVY
AAAPVGRFTAHWRVPLLTAGAPALGFGVKDEYALTTRAGPSYAKLGDFVAALHRRLGWER
QALMLYAYRPGDEEHCFFLVEGLFMRVRDRLNITVDHLEFAEDDLSHYTRLLRTMPRKGR
VIYICSSPDAFRTLMLLALEAGLCGEDYVFFHLDIFGQSLQGGQGPAPRRPWERGDGQDV
SARQAFQAAKIITYKDPDNPEYLEFLKQLKHLAYEQFNFTMEDGLVNTIPASFHDGLLLY
IQAVTETLAHGGTVTDGENITQRMWNRSFQGVTGYLKIDSSGDRETDFSLWDMDPENGAF
RVVLNYNGTSQELVAVSGRKLNWPLGYPPPDIPKCGFDNEDPACNQDHLSTLEVLALVGS
LSLLGILIVSFFIYRKMQLEKELASELWRVRWEDVEPSSLERHLRSAGSRLTLSGRGSNY
GSLLTTEGQFQVFAKTAYYKGNLVAVKRVNRKRIELTRKVLFELKHMRDVQNEHLTRFVG
ACTDPPNICILTEYCPRGSLQDILENESITLDWMFRYSLTNDIVKGMLFLHNGAICSHGN
LKSSNCVVDGRFVLKITDYGLESFRDLDPEQGHTVYAKKLWTAPELLRMASPPVRGSQAG
DVYSFGIILQEIALRSGVFHVEGLDLSPKEIIERVTRGEQPPFRPSLALQSHLEELGLLM
QRCWAEDPQERPPFQQIRLTLRKFNRENSSNILDNLLSRMEQYANNLEELVEERTQAYLE
EKRKAEALLYQILPHSVAEQLKRGETVQAEAFDSVTIYFSDIVGFTALSAESTPMQVVTL
LNDLYTCFDAVIDNFDVYKVETIGDAYMVVSGLPVRNGRLHACEVARMALALLDAVRSFR
IRHRPQEQLRLRIGIHTGPVCAGVVGLKMPRYCLFGDTVNTASRMESNGEALKIHLSSET
KAVLEEFGGFELELRGDVEMKGKGKVRTYWLLGERGSSTRG
Target 1 Number of Residues 1078
Target 1 Molecular Weight 118921
Target 1 Theoretical pI 6.61
Target 1 GO Classification
Function
protein-tyrosine kinase activity
binding
nucleotide binding
purine nucleotide binding
adenyl nucleotide binding
ATP binding
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
protein kinase activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
peptide receptor activity, G-protein coupled
catalytic activity
lyase activity
phosphorus-oxygen lyase activity
Process
macromolecule metabolism
biopolymer metabolism
biopolymer modification
protein modification
protein amino acid phosphorylation
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
nucleotide metabolism
nucleotide biosynthesis
cyclic nucleotide biosynthesis
cellular process
cell communication
signal transduction
intracellular signaling cascade
Component
cell
membrane
Target 1 General Function Signal transduction mechanisms
Target 1 Specific Function Receptor for atrial natriuretic peptide. Has guanylate cyclase activity on binding of ANF
Target 1 Pathways
Name SMPDB Link KEGG Link
Purine metabolism SMP00050 Link Image map00230 Link Image
Target 1 Reactions
  • GTP = 3',5'-cyclic GMP + diphosphate
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-32
Target 1 Transmembrane Regions
  • 474-494
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 28230 Link Image
Target 1 UniProtKB/Swiss-Prot ID P16066 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ANPRA_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • single-pass type I membrane protein
Target 1 Gene Sequence >3186 bp 
ATGCCGGGGCCCCGGCGCCCCGCTGGCTCCCGCCTGCGCCTGCTCCTGCTCCTGCTGCTG
CCGCCGCTGCTGCTGCTGCTCCGGGGCAGCCACGCGGGCAACCTGACGGTAGCCGTGGTA
CTGCCGCTGGCCAATACCTCGTACCCCTGGTCGTGGGCGCGCGTGGGACCCGCCGTGGAG
CTGGCCCTGGCCCAGGTGAAGGCGCGCCCCGACTTGCTGCCGGGCTGGACGGTCCGCACG
GTGCTGGGCAGCAGCGAAAACGCGCTGGGCGTCTGCTCCGACACCGCAGCGCCCCTGGCC
GCGGTGGACCTCAAGTGGGAGCACAACCCCGCTGTGTTCCTGGGCCCCGGCTGCGTGTAC
GCCGCCGCCCCAGTGGGGCGCTTCACCGCGCACTGGCGGGTCCCGCTGCTGACCGCCGGC
GCCCCGGCGCTGGGCTTCGGTGTCAAGGACGAGTATGCGCTGACCACCCGCGCGGGGCCC
AGCTACGCCAAGCTGGGGGACTTCGTGGCGGCGCTGCACCGACGGCTGGGCTGGGAGCGC
CAAGCGCTCATGCTCTACGCCTACCGGCCGGGTGACGAAGAGCACTGCTTCTTCCTCGTG
GAGGGGCTGTTCATGCGGGTCCGCGACCGCCTCAATATTACGGTGGACCACCTGGAGTTC
GCCGAGGACGACCTCAGCCACTACACCAGGCTGCTGCGGACCATGCCGCGCAAAGGCCGA
GTTATCTACATCTGCAGCTCCCCTGATGCCTTCAGAACCCTCATGCTCCTGGCCCTGGAA
GCTGGCTTGTGTGGGGAGGACTACGTTTTCTTCCACCTGGATATCTTTGGGCAAAGCCTG
CAAGGTGGACAGGGCCCTGCTCCCCGCAGGCCCTGGGAGAGAGGGGATGGGCAGGATGTC
AGTGCCCGCCAGGCCTTTCAGGCTGCCAAAATCATTACATATAAAGACCCAGATAATCCC
GAGTACTTGGAATTCCTGAAGCAGTTAAAACACCTGGCCTATGAGCAGTTCAACTTCACC
ATGGAGGATGGCCTGGTGAACACCATCCCAGCATCCTTCCACGACGGGCTCCTGCTCTAT
ATCCAGGCAGTGACGGAGACTCTGGCACATGGGGGAACTGTTACTGATGGGGAGAACATC
ACTCAGCGGATGTGGAACCGAAGCTTTCAAGGTGTGACAGGATACCTGAAAATTGATAGC
AGTGGCGATCGGGAAACAGACTTCTCCCTCTGGGATATGGATCCCGAGAATGGTGCCTTC
AGGGTTGTACTGAACTACAATGGGACTTCCCAAGAGCTGGTGGCTGTGTCGGGGCGCAAA
CTGAACTGGCCCCTGGGGTACCCTCCTCCTGACATCCCCAAATGTGGCTTTGACAACGAA
GACCCAGCATGCAACCAAGATCACCTTTCCACCCTGGAGGTGCTGGCTTTGGTGGGCAGC
CTCTCCTTGCTCGGCATTCTGATTGTCTCCTTCTTCATATACAGGAAGATGCAGCTGGAG
AAGGAACTGGCCTCGGAGCTGTGGCGGGTGCGCTGGGAGGACGTTGAGCCCAGTAGCCTT
GAGAGGCACCTGCGGAGTGCAGGCAGCCGGCTGACCCTGAGCGGGAGAGGCTCCAATTAC
GGCTCCCTGCTAACCACAGAGGGCCAGTTCCAAGTCTTTGCCAAGACAGCATATTATAAG
GGCAACCTCGTGGCTGTGAAACGTGTGAACCGTAAACGCATTGAGCTGACACGAAAAGTC
CTGTTTGAACTGAAGCATATGCGGGATGTGCAGAATGAACACCTGACCAGGTTTGTGGGA
GCCTGCACCGACCCCCCCAATATCTGCATCCTCACAGAGTACTGTCCCCGTGGGAGCCTG
CAGGACATTCTGGAGAATGAGAGCATCACCCTGGACTGGATGTTCCGGTACTCACTCACC
AATGACATCGTCAAGGGCATGCTGTTTCTACACAATGGGGCTATCTGTTCCCATGGGAAC
CTCAAGTCATCCAACTGCGTGGTAGATGGGCGCTTTGTGCTCAAGATCACCGACTATGGG
CTGGAGAGCTTCAGGGACCTGGACCCAGAGCAAGGACACACCGTTTATGCCAAAAAGCTG
TGGACGGCCCCTGAGCTCCTGCGAATGGCTTCACCCCCTGTGCGGGGCTCCCAGGCTGGT
GACGTATACAGCTTTGGGATCATCCTTCAGGAGATTGCCCTGAGGAGTGGGGTCTTCCAC
GTGGAAGGTTTGGACCTGAGCCCCAAAGAGATCATCGAGCGGGTGACTCGGGGTGAGCAG
CCCCCCTTCCGGCCCTCCCTGGCCCTGCAGAGTCACCTGGAGGAGTTGGGGCTGCTCATG
CAGCGGTGCTGGGCTGAGGACCCACAGGAGAGGCCACCATTCCAGCAGATCCGCCTGACG
TTGCGCAAATTTAACAGGGAGAACAGCAGCAACATCCTGGACAACCTGCTGTCCCGCATG
GAGCAGTACGCGAACAATCTGGAGGAACTGGTGGAGGAGCGGACCCAGGCATACCTGGAG
GAGAAGCGCAAGGCTGAGGCCCTGCTCTACCAGATCCTGCCTCACTCAGTGGCTGAGCAG
CTGAAGCGTGGGGAGACGGTGCAGGCCGAAGCCTTTGACAGTGTTACCATCTACTTCAGT
GACATTGTGGGTTTCACAGCGCTGTCGGCGGAGAGCACACCCATGCAGGTGGTGACCCTG
CTCAATGACCTGTACACTTGCTTTGATGCTGTCATAGACAACTTTGATGTGTACAAGGTG
GAGACAATTGGCGATGCCTACATGGTGGTGTCAGGGCTCCCTGTGCGGAACGGGCGGCTA
CACGCCTGCGAGGTAGCCCGCATGGCCCTGGCACTGCTGGATGCTGTGCGCTCCTTCCGA
ATCCGCCACCGGCCCCAGGAGCAGCTGCGCTTGCGCATTGGCATCCACACAGGACCTGTG
TGTGCTGGAGTGGTGGGACTGAAGATGCCCCGTTACTGTCTCTTTGGGGATACAGTCAAC
ACAGCCTCAAGAATGGAGTCTAATGGGGAAGCCCTGAAGATCCACTTGTCTTCTGAGACC
AAGGCTGTCCTGGAGGAGTTTGGTGGTTTCGAGCTGGAGCTTCGAGGGGATGTAGAAATG
AAGGGCAAAGGCAAGGTTCGGACCTACTGGCTCCTTGGGGAGAGGGGGAGTAGCACCCGA
GGCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID NPR1 Link Image
Target 1 GenAtlas ID NPR1 Link Image
Target 1 HGNC ID HGNC:7943 Link Image
Target 1 Chromosome Location 1
Target 1 Locus 1q21-q22
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Lowe DG, Chang MS, Hellmiss R, Chen E, Singh S, Garbers DL, Goeddel DV: Human atrial natriuretic peptide receptor defines a new paradigm for second messenger signal transduction. EMBO J. 1989 May;8(5):1377-84. [PubMed Link Image]
  2. Pardhasaradhi K, Kutty RK, Gentleman S, Krishna G: Expression of mRNA for atrial natriuretic peptide receptor guanylate cyclase (ANPRA) in human retina. Cell Mol Neurobiol. 1994 Feb;14(1):1-7. [PubMed Link Image]
  3. Takahashi Y, Nakayama T, Soma M, Izumi Y, Kanmatsuse K: Organization of the human natriuretic peptide receptor A gene. Biochem Biophys Res Commun. 1998 May 29;246(3):736-9. [PubMed Link Image]
Target 1 Drug References
  1. 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 Link Image]
  2. 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 Link Image]
  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 Link Image]
  4. 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 Link Image]
  5. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

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