Diazoxide

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Diazoxide
Diazoxide.svg
Clinical data
Trade names Proglycem, others
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • AU:C
Routes of
administration 		By mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding 90%
Metabolism Liver oxidation and sulfate conjugation
Elimination half-life 21-45 hours
Excretion Kidney
Identifiers
  • 7-Chloro-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.006.063 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C8H7ClN2O2S
Molar mass 230.67 g·mol−1
3D model (JSmol)
Melting point 330 to 331 °C (626 to 628 °F)
  • Clc1ccc2c(c1)S(=O)(=O)/N=C(\N2)C
  • InChI=1S/C8H7ClN2O2S/c1-5-10-7-3-2-6(9)4-8(7)14(12,13)11-5/h2-4H,1H3,(H,10,11) Yes check.svgY
  • Key:GDLBFKVLRPITMI-UHFFFAOYSA-N Yes check.svgY
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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. [4] This includes islet cell tumors that cannot be removed and leucine sensitivity. [4] It can also be used in refractory cases of sulfonylurea toxicity. [5] It is taken by mouth. [4]

Contents

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. [3] It was approved for this use in the United States in March 2025. [6]

Common side effects include high blood sugar, fluid retention, low blood platelets, a fast heart rate, increased hair growth, and nausea. [4] Other severe side effects include pulmonary hypertension and heart failure. [4] It is chemically similar to thiazide diuretics. [4] It works by decreasing insulin release from the pancreas and increasing glucose release by the liver. [4]

Diazoxide was approved for medical use in the United States in 1973. [4] It is on the World Health Organization's List of Essential Medicines. [7] It is available as a generic medication. [8]

Medical uses

Diazoxide is used as a vasodilator in the treatment of acute hypertension or malignant hypertension. [9]

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) [10] or congenital hyperinsulinism.

Diazoxide acts as a positive allosteric modulator of the AMPA and kainate receptors, suggesting potential application as a cognitive enhancer. [11]

Side effects

Diazoxide interferes with insulin release through its action on potassium channels. [12] 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. [5]

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. [13]

Diazoxide has been associated with development of hypertrichosis and stimulation of scalp hair growth. [14] [15]

Research

Diazoxide, formulated as its choline salt diazoxide choline, is an experimental antiobesity drug being tested in people with Prader-Willi syndrome [16] [17] [18] and monogenic obesity caused by mutations in the SH2B1, PCSK1, or SIM1 genes. [19]

References

  1. ↑ "Product monograph brand safety updates". Health Canada . 7 July 2016. Retrieved 3 April 2024.
  2. ↑ "Proglycem- diazoxide suspension". DailyMed. 19 July 2024. Retrieved 28 March 2025.
  3. 1 2 "Vykat XR- diazoxide choline tablet, film coated". DailyMed. 26 March 2025. Retrieved 17 April 2025.
  4. 1 2 3 4 5 6 7 8 "Diazoxide Monograph for Professionals". Drugs.com. Retrieved 11 October 2019.
  5. 1 2 Doyle ME, Egan JM (March 2003). "Pharmacological agents that directly modulate insulin secretion". Pharmacological Reviews. 55 (1): 105–131. doi:10.1124/pr.55.1.7. PMID   12615955. S2CID   11121340.
  6. ↑ "Soleno Therapeutics Announces U.S. FDA Approval of Vykat XR to Treat Hyperphagia in Prader-Willi Syndrome" (Press release). Soleno Therapeutics. 26 March 2025. Retrieved 28 March 2025– via GlobeNewswire.
  7. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  8. ↑ British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 708. ISBN   9780857113382.
  9. ↑ van Hamersvelt HW, Kloke HJ, de Jong DJ, Koene RA, Huysmans FT (August 1996). "Oedema formation with the vasodilators nifedipine and diazoxide: direct local effect or sodium retention?". Journal of Hypertension. 14 (8): 1041–1045. doi:10.1097/00004872-199608000-00016. PMID   8884561. S2CID   3283469. Closed Access logo transparent.svg
  10. ↑ Huang Q, Bu S, Yu Y, Guo Z, Ghatnekar G, Bu M, et al. (January 2007). "Diazoxide prevents diabetes through inhibiting pancreatic beta-cells from apoptosis via Bcl-2/Bax rate and p38-beta mitogen-activated protein kinase". Endocrinology. 148 (1): 81–91. doi: 10.1210/en.2006-0738 . PMID   17053028. Open Access logo PLoS transparent.svg
  11. ↑ Randle JC, Biton C, Lepagnol JM (November 1993). "Allosteric potentiation by diazoxide of AMPA receptor currents and synaptic potentials". European Journal of Pharmacology. 247 (3): 257–265. doi:10.1016/0922-4106(93)90193-D. PMID   8307099. Closed Access logo transparent.svg
  12. ↑ Panten U, Burgfeld J, Goerke F, Rennicke M, Schwanstecher M, Wallasch A, et al. (April 1989). "Control of insulin secretion by sulfonylureas, meglitinide and diazoxide in relation to their binding to the sulfonylurea receptor in pancreatic islets". Biochemical Pharmacology. 38 (8): 1217–1229. doi:10.1016/0006-2952(89)90327-4. PMID   2650685.
  13. ↑ "FDA Drug Safety Communication: FDA warns about a serious lung condition in infants and newborns treated with Proglycem (diazoxide)" (Press release). U.S. Food and Drug Administration (FDA). 16 July 2015. Archived from the original on 19 July 2015. Retrieved 19 July 2015.
  14. ↑ Rossi A, Cantisani C, Melis L, Iorio A, Scali E, Calvieri S (May 2012). "Minoxidil use in dermatology, side effects and recent patents". Recent Pat Inflamm Allergy Drug Discov. 6 (2): 130–136. doi:10.2174/187221312800166859. PMID   22409453. Other potassium channel openers, like diazoxide [39, 40] and pinacidil [41] can cause hypertrichosis in humans as well as minoxidil. In balding macaques minoxidil, cromakalin and P-1075 (a pinacidil analogue) stimulate hair growth in about 20 weeks of topical treatment, whereas a fourth potassium channel opener, called RP49356, is not effective [42].
  15. ↑ Buhl AE, Conrad SJ, Waldon DJ, Brunden MN (July 1993). "Potassium channel conductance as a control mechanism in hair follicles". J Invest Dermatol. 101 (1 Suppl): 148S –152S. doi:10.1111/1523-1747.ep12363290. PMID   8326149. The evidence that [potassium channel openers (PCOs)] are active on hair growth is correlative. In humans three PCOs have been reported to affect hair growth. Minoxidil was reported to induce hypertrichosis during early clinical trials as an antihypertensive [12]. These side effects were characterized by increasingly visual facial hair, thickening of eyebrows, and diffuse hair growth across the upper back and limbs. Systemic minoxidil induced hypertrichosis in 80–100% of adults [13]. Clinical trials using topical minoxidil demonstrate increased scalp hair in about 39% of treated balding men. Oral diazoxide causes hypertrichosis in most hypoglycemic children and about 1% of adults, and induces some scalp hair in 25% of the balding patients [13–15]. Systemic pinacidil induces hypertrichosis in 2–13% of patients [13]. We are not aware of any topical hair growth trials using pinacidil.
  16. ↑ Miller JL, Gevers E, Bridges N, Yanovski JA, Salehi P, Obrynba KS, et al. (February 2024). "Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study". Obesity. 32 (2): 252–261. doi: 10.1002/oby.23928 . hdl: 10044/1/107689 . PMC   12181816 . PMID   37919617. S2CID   264973612.
  17. ↑ Kimonis V, Surampalli A, Wencel M, Gold JA, Cowen NM (23 September 2019). "A randomized pilot efficacy and safety trial of diazoxide choline controlled-release in patients with Prader-Willi syndrome". PLOS ONE. 14 (9): e0221615. Bibcode:2019PLoSO..1421615K. doi: 10.1371/journal.pone.0221615 . PMC   6756513 . PMID   31545799.
  18. ↑ Miller JL, Gevers E, Bridges N, Yanovski JA, Salehi P, Obrynba KS, et al. (June 2023). "Diazoxide Choline Extended-Release Tablet in People With Prader-Willi Syndrome: A Double-Blind, Placebo-Controlled Trial". The Journal of Clinical Endocrinology and Metabolism. 108 (7): 1676–1685. doi:10.1210/clinem/dgad014. PMC   10271219 . PMID   36639249.
  19. ↑ Clinical trial number NCT05532020 for "An Open-Label Study of Diazoxide Choline in Patients With Genetic Obesities" at ClinicalTrials.gov
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