| 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 |
|
| Name |
Isosorbide Dinitrate |
| Drug Type |
|
| 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 |
- 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 Mixtures |
- 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 |
 |
| 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  |
| KEGG Compound |
C07456  |
| PubChem Compound |
6883  |
| PubChem Substance |
7979661  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA450125  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
00670944  |
| RxList Link |
http://www.rxlist.com/cgi/generic2/isodinit.htm  |
| PDRhealth Link |
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/iso1212.shtml  |
| 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 | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 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 |
|
| 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  |
| Contraindications |
Show  |
| Interactions |
Show  |
| 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 |
- Drugs.com

- RxList

- PDRhealth

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 3A4 (CYP3A4)
|
| Targets |
- Atrial natriuretic peptide receptor A
|
|
Drug Target 1
[top]
|
| Target 1 ID |
613 |
| Target 1 Name |
Atrial natriuretic peptide receptor A |
| Target 1 Synonyms |
- ANP-A
- ANPRA
- Atrial natriuretic peptide A-type receptor
- Atrial natriuretic peptide receptor A precursor
- EC 4.6.1.2
- GC-A
- Guanylate cyclase
- 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 |
|
| Target 1 Reactions |
- GTP = 3',5'-cyclic GMP + diphosphate
|
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
28230  |
| Target 1 UniProtKB/Swiss-Prot ID |
P16066  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
ANPRA_HUMAN  |
| 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  |
| Target 1 GenAtlas ID |
NPR1  |
| Target 1 HGNC ID |
HGNC:7943  |
| Target 1 Chromosome Location |
1 |
| Target 1 Locus |
1q21-q22 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- 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
]
- 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
]
- 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
]
|
| Target 1 Drug References |
- 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
]
- 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
]
- 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
]
- 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
]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed
]
|