View source for Isosorbide dinitrate

{{Short description|Chemical compound}}
{{Use dmy dates|date=February 2024}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 477495637
| image = Isosorbide dinitrate structure.svg
| image_class = skin-invert-image
| width = 192
| alt = 
| image2 = Isosorbide-dinitrate-from-xtal-3D-bs-17.png
| image_class2 = bg-transparent
| alt2 = 

<!-- Clinical data -->
| tradename = Isordil, others<ref name=AHFS2016/>
| Drugs.com = {{drugs.com|monograph|isosorbide-dinitrate-mononitrate}}
| MedlinePlus = a682348
| DailyMedID = Isosorbide dinitrate
| pregnancy_AU = B1
| legal_status = Rx-only
| routes_of_administration = [[Oral administration|By mouth]]

<!-- Pharmacokinetic data -->
| bioavailability = 10–90%, average 25%
| metabolism = [[Liver]]
| elimination_half-life = 1 hour
| excretion = [[Kidney]]

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 87-33-2
| ATC_prefix = C01
| ATC_suffix = DA08
| ATC_supplemental = {{ATC|C05|AE02}}
| PubChem = 6883
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00883
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 6619
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 2171310
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = IA7306519N
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00516
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 6061
| synonyms = ISDN; (3''R'',3a''S'',6''S'',6a''S'')-hexahydrofuro[3,2-''b'']furan-3,6-diyl dinitrate

<!-- Chemical data -->
| IUPAC_name = 1,4:3,6-dianhydro-2,5-di-''O''-nitro-<small>D</small>-glucitol
| C=6 | H=8 | N=2 | O=8
| SMILES = [O-][N+](=O)O[C@H]1[C@H]2OC[C@H](O[N+]([O-])=O)[C@H]2OC1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MOYKHGMNXAOIAT-JGWLITMVSA-N
}}
<!-- Definition and medical uses -->
'''Isosorbide dinitrate''' is a medication used for [[heart failure]], [[esophageal spasms]], and to treat and prevent [[angina pectoris]].<ref name=AHFS2016/> It has been found to be particularly useful in heart failure due to [[systolic dysfunction]] together with [[hydralazine]].<ref>{{cite journal | vauthors = Chavey WE, Bleske BE, Van Harrison R, Hogikyan RV, Kesterson SK, Nicklas JM | title = Pharmacologic management of heart failure caused by systolic dysfunction | journal = American Family Physician | volume = 77 | issue = 7 | pages = 957–964 | date = April 2008 | pmid = 18441861 }}</ref><ref name=AHFS2016/> It is taken [[Oral administration|by mouth]] or under the tongue.<ref name=AHFS2016>{{cite web|title=Isosorbide Dinitrate/Mononitrate|url=https://www.drugs.com/monograph/isosorbide-dinitrate-mononitrate.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221004406/https://www.drugs.com/monograph/isosorbide-dinitrate-mononitrate.html|archive-date=21 December 2016}}</ref>

<!-- Side effects and mechanism -->
Common side effects include [[headache]], [[postural hypotension|lightheadedness with standing]], and [[blurred vision]].<ref name=AHFS2016/> Severe side effects include [[low blood pressure]].<ref name=AHFS2016/> It is unclear if use in [[pregnancy]] is safe for the baby.<ref name=AHFS2016/> It should not be used together with [[PDE5 inhibitor|PDE5 Inhibitors]].<ref name=AHFS2016/> Isosorbide dinitrate is in the [[nitrate (pharmacology)|nitrate]] family of medications and works by [[vasodilation|dilating blood vessels]].<ref name=AHFS2016/>

<!-- Society and culture -->
Isosorbide dinitrate was first written about in 1939.<ref name=Fis2006>{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=454|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA454|language=en|url-status=live|archive-url=https://web.archive.org/web/20161220113902/https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA454|archive-date=20 December 2016}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> Isosorbide dinitrate is available as a [[generic medication]].<ref name=AHFS2016/><ref>{{cite web | title=Competitive Generic Therapy Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=29 June 2023 | url=https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | access-date=29 June 2023 | archive-date=29 June 2023 | archive-url=https://web.archive.org/web/20230629233651/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | url-status=dead }}</ref> A long-acting form exists.<ref name=AHFS2016/> In 2023, isosorbide was the 125th most commonly prescribed medication in the United States, with more than 5{{nbsp}}million prescriptions.<ref name="Top 300">{{cite web | title=Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Isosorbide Drug Usage Statistics, United States, 2013–2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Isosorbide | access-date = 18 August 2025 }}</ref>

==Medical uses==
It is used for angina, in addition to other medications for congestive heart failure, and for esophageal spasms.<ref name="AHFS2016"/> It is available as an oral tablet both in extended release and slow release. The onset of action for Isosorbide Dinitrate is thirty minutes and the onset of action for oral extended release is 12–24 hours.

Long-acting nitrates can be more useful as they are generally more effective and stable in the short term.

==Side effects==
===Tolerance===
After long-term use for treating chronic conditions, tolerance may develop in patients, reducing its effectiveness.  The mechanisms of [[nitrate tolerance]] have been thoroughly investigated in the last 30 years and several hypotheses have been proposed. These include: 
# Impaired biotransformation of isosorbide dinitrate to its active principle NO (or a NO-related species)
# Neurohormonal activation, causing sympathetic activation and release of vasoconstrictors such as endothelin and angiotensin II which counteract the vasodilation induced by isosorbide dinitrate
# Plasma volume expansion
# The oxidative stress hypothesis<ref name="pmid7814613">{{cite journal | vauthors = Münzel T, Sayegh H, Freeman BA, Tarpey MM, Harrison DG | title = Evidence for enhanced vascular superoxide anion production in nitrate tolerance. A novel mechanism underlying tolerance and cross-tolerance | journal = The Journal of Clinical Investigation | volume = 95 | issue = 1 | pages = 187–94 | date = January 1995 | pmid = 7814613 | pmc = 295403 | doi = 10.1172/JCI117637 }}</ref>

The last hypothesis might represent a unifying hypothesis, and an isosorbide dinitrate-induced inappropriate production of oxygen free radicals might induce a number of abnormalities which include the ones described above. 
Furthermore, nitrate tolerance is shown to be associated with vascular abnormalities which have the potential to worsen patients prognosis:<ref name="pmid10467211">{{cite journal | vauthors = Nakamura Y, Moss AJ, Brown MW, Kinoshita M, Kawai C | title = Long-term nitrate use may be deleterious in ischemic heart disease: A study using the databases from two large-scale postinfarction studies. Multicenter Myocardial Ischemia Research Group | journal = American Heart Journal | volume = 138 | issue = 3 Pt 1 | pages = 577–85 | date = September 1999 | pmid = 10467211 | doi = 10.1016/s0002-8703(99)70163-8 | url = }}</ref> these include endothelial and autonomic dysfunction.<ref name="pmid18634978">{{cite journal | vauthors = Gori T, Parker JD | title = Nitrate-induced toxicity and preconditioning: a rationale for reconsidering the use of these drugs | journal = Journal of the American College of Cardiology | volume = 52 | issue = 4 | pages = 251–4 | date = July 2008 | pmid = 18634978 | doi = 10.1016/j.jacc.2008.04.019 }}</ref>  

==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]] ([[cyclic guanosine 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 sequestration of calcium ions results in the relaxation of the smooth muscle cells and vasodilation.<ref>{{cite book | vauthors = Rang HP, Ritter J, Flower RJ, Henderson G |title=Pharmacology |publisher=Elsevier |isbn=978-0-7020-5362-7 |pages=261 |edition=8th | date = 2016 }}</ref>

==Society and culture==
Isosorbide dinitrate is sold in the US under the brand names Dilatrate-SR by [[Schwarz Pharma|Schwarz]] and Isordil by [[Valeant Pharmaceuticals|Valeant]], according to [[Approved Drug Products with Therapeutic Equivalence Evaluations|FDA Orange Book]]. It is sold under the trade name Isoket in the United Kingdom, Argentina, and Hong Kong. It is also a component of [[BiDil]].

== References==
{{reflist}}

{{Antianginals (nitrates)}}
{{Preparations for treatment of wounds and ulcers}}
{{Nitric oxide signaling}}
{{Portal bar|Medicine}}

[[Category:Nitrate esters]]
[[Category:Antianginals]]
[[Category:Furofurans]]
[[Category:World Health Organization essential medicines]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Drugs developed by Wyeth]]
[[Category:Drugs developed by Pfizer]]