diazoxide
{{Short description|Medication used to treat low blood sugar and high blood pressure}}
{{Use dmy dates|date=March 2025}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 460781978
| image = Diazoxide.svg
| image_class = skin-invert-image
| alt =
| tradename = Proglycem, others
| Drugs.com = {{drugs.com|monograph|diazoxide}}
| DailyMedID = Diazoxide
| pregnancy_AU = C
| routes_of_administration = By mouth, intravenous
| ATC_prefix = C02
| ATC_suffix = DA01
| ATC_supplemental = {{ATC|V03|AH01}}
| legal_CA = Rx-only
| legal_CA_comment = {{cite web | title=Product monograph brand safety updates | website=Health Canada | date=7 July 2016 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=3 April 2024}}
| legal_UK = POM
| legal_US = Rx-only
| legal_US_comment = {{cite web | title=Proglycem- diazoxide suspension | website=DailyMed | date=19 July 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b16c7832-2fd9-49af-b923-1dc0d91fd6e2 | access-date=28 March 2025}}
| bioavailability =
| protein_bound = 90%
| metabolism = Liver oxidation and sulfate conjugation
| elimination_half-life = 21-45 hours
| excretion = Kidney
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 364-98-7
| PubChem = 3019
| IUPHAR_ligand = 2409
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01119
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2911
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = O5CB12L4FN
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00294
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 4495
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 181
| IUPAC_name = 7-Chloro-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
| C=8 | H=7 | Cl=1 | N=2 | O=2 | S=1
| smiles = Clc1ccc2c(c1)S(=O)(=O)/N=C(\N2)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C8H7ClN2O2S/c1-5-10-7-3-2-6(9)4-8(7)14(12,13)11-5/h2-4H,1H3,(H,10,11)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = GDLBFKVLRPITMI-UHFFFAOYSA-N
| melting_point = 330
| melting_high = 331
}}
Diazoxide, sold under the brand name Proglycem among others, is a medication used to treat low blood sugar due to a number of specific causes.{{cite web |title=Diazoxide Monograph for Professionals |url=https://www.drugs.com/monograph/diazoxide.html |website=Drugs.com |access-date=11 October 2019 }} This includes islet cell tumors that cannot be removed and leucine sensitivity. It can also be used in refractory cases of sulfonylurea toxicity.{{cite journal | vauthors = Doyle ME, Egan JM | title = Pharmacological agents that directly modulate insulin secretion | journal = Pharmacological Reviews | volume = 55 | issue = 1 | pages = 105–131 | date = March 2003 | pmid = 12615955 | doi = 10.1124/pr.55.1.7 | s2cid = 11121340 }} It is taken by mouth.
Diazoxide, used as the salt diazoxide choline, and sold under the brand name Vykat XR, is used for the treatment of hyperphagia in people with Prader-Willi syndrome.{{cite web | title=Vykat XR- diazoxide choline tablet, film coated | website=DailyMed | date=26 March 2025 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e745e85-9512-e360-e063-6394a90aebf1 | access-date=17 April 2025}} It was approved for this use in the United States in March 2025.{{cite press release | title=Soleno Therapeutics Announces U.S. FDA Approval of Vykat XR to Treat Hyperphagia in Prader-Willi Syndrome | publisher=Soleno Therapeutics | via=GlobeNewswire | date=26 March 2025 | url=https://www.globenewswire.com/news-release/2025/03/26/3050184/0/en/index.html | access-date=28 March 2025}}
Common side effects include high blood sugar, fluid retention, low blood platelets, a fast heart rate, increased hair growth, and nausea. Other severe side effects include pulmonary hypertension and heart failure. It is chemically similar to thiazide diuretics. It works by decreasing insulin release from the pancreas and increasing glucose release by the liver.
Diazoxide was approved for medical use in the United States in 1973. It is on the World Health Organization's List of Essential Medicines.{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }} It is available as a generic medication.{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=708|edition=76}}
Medical uses
Diazoxide is used as a vasodilator in the treatment of acute hypertension or malignant hypertension.{{cite journal | vauthors = van Hamersvelt HW, Kloke HJ, de Jong DJ, Koene RA, Huysmans FT | title = Oedema formation with the vasodilators nifedipine and diazoxide: direct local effect or sodium retention? | journal = Journal of Hypertension | volume = 14 | issue = 8 | pages = 1041–1045 | date = August 1996 | pmid = 8884561 | doi = 10.1097/00004872-199608000-00016 | s2cid = 3283469 }}{{closed access}}
Diazoxide also inhibits the secretion of insulin by opening ATP-sensitive potassium channel of beta cells of the pancreas; thus, it is used to counter hypoglycemia in disease states such as insulinoma (a tumor producing insulin){{cite journal | vauthors = Huang Q, Bu S, Yu Y, Guo Z, Ghatnekar G, Bu M, Yang L, Lu B, Feng Z, Liu S, Wang F | title = Diazoxide prevents diabetes through inhibiting pancreatic beta-cells from apoptosis via Bcl-2/Bax rate and p38-beta mitogen-activated protein kinase | journal = Endocrinology | volume = 148 | issue = 1 | pages = 81–91 | date = January 2007 | pmid = 17053028 | doi = 10.1210/en.2006-0738 | doi-access = free }}{{open access}} or congenital hyperinsulinism.
Diazoxide acts as a positive allosteric modulator of the AMPA and kainate receptors, suggesting potential application as a cognitive enhancer.{{cite journal | vauthors = Randle JC, Biton C, Lepagnol JM | title = Allosteric potentiation by diazoxide of AMPA receptor currents and synaptic potentials | journal = European Journal of Pharmacology | volume = 247 | issue = 3 | pages = 257–265 | date = November 1993 | pmid = 8307099 | doi = 10.1016/0922-4106(93)90193-D }}{{closed access}}
Side effects
Diazoxide interferes with insulin release through its action on potassium channels.{{cite journal | vauthors = Panten U, Burgfeld J, Goerke F, Rennicke M, Schwanstecher M, Wallasch A, Zünkler BJ, Lenzen S | title = Control of insulin secretion by sulfonylureas, meglitinide and diazoxide in relation to their binding to the sulfonylurea receptor in pancreatic islets | journal = Biochemical Pharmacology | volume = 38 | issue = 8 | pages = 1217–1229 | date = April 1989 | pmid = 2650685 | doi = 10.1016/0006-2952(89)90327-4 }} Diazoxide is one of the most potent openers of the K+ ATP channels present on the insulin producing beta cells of the pancreas. Opening these channels leads to hyperpolarization of cell membrane, a decrease in calcium influx, and a subsequently reduced release of insulin.
The US Food and Drug Administration (FDA) published a safety announcement in July 2015 highlighting the potential for development of pulmonary hypertension in newborns and infants treated with this drug.{{Cite press release|title = FDA Drug Safety Communication: FDA warns about a serious lung condition in infants and newborns treated with Proglycem (diazoxide)|date = 16 July 2015|publisher = U.S. Food and Drug Administration (FDA) |url = https://www.fda.gov/Drugs/DrugSafety/ucm454833.htm|access-date = 19 July 2015}}
Research
Diazoxide, formulated as its choline salt diazoxide choline, is an experimental antiobesity drug being tested in people with Prader-Willi syndrome{{cite journal | vauthors = Miller JL, Gevers E, Bridges N, Yanovski JA, Salehi P, Obrynba KS, Felner EI, Bird LM, Shoemaker AH, Angulo M, Butler MG, Stevenson D, Goldstone AP, Wilding J, Lah M, Shaikh MG, Littlejohn E, Abuzzahab MJ, Fleischman A, Hirano P, Yen K, Cowen NM, Bhatnagar A | title = Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study | journal = Obesity | volume = 32 | issue = 2 | pages = 252–261 | date = February 2024 | pmid = 37919617 | doi = 10.1002/oby.23928 | hdl-access = free | s2cid = 264973612 | doi-access = free | hdl = 10044/1/107689 }}{{cite journal | vauthors = Kimonis V, Surampalli A, Wencel M, Gold JA, Cowen NM | title = A randomized pilot efficacy and safety trial of diazoxide choline controlled-release in patients with Prader-Willi syndrome | journal = PLOS ONE | volume = 14 | issue = 9 | pages = e0221615 | date = 23 September 2019 | pmid = 31545799 | pmc = 6756513 | doi = 10.1371/journal.pone.0221615 | doi-access = free | bibcode = 2019PLoSO..1421615K }}{{cite journal | vauthors = Miller JL, Gevers E, Bridges N, Yanovski JA, Salehi P, Obrynba KS, Felner EI, Bird LM, Shoemaker AH, Angulo M, Butler MG, Stevenson D, Abuzzahab J, Barrett T, Lah M, Littlejohn E, Mathew V, Cowen NM, Bhatnagar A | title = Diazoxide Choline Extended-Release Tablet in People With Prader-Willi Syndrome: A Double-Blind, Placebo-Controlled Trial | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 108 | issue = 7 | pages = 1676–1685 | date = June 2023 | pmid = 36639249 | pmc = 10271219 | doi = 10.1210/clinem/dgad014 }} and monogenic obesity caused by mutations in the SH2B1, PCSK1, or SIM1 genes.{{ClinicalTrialsGov|NCT05532020|An Open-Label Study of Diazoxide Choline in Patients With Genetic Obesities}}
References
{{Reflist}}
{{Nonsympatholytic vasodilatory antihypertensives}}
{{Other therapeutic products}}
{{Ion channel modulators}}
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Category:Carbonic anhydrase inhibitors
Category:Potassium channel openers
Category:AMPA receptor positive allosteric modulators
Category:Kainate receptor agonists
Category:World Health Organization essential medicines