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Diazoxide

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Diazoxide
Clinical data
Trade namesProglycem, Vykat XR, others
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: C
Routes of
administration		Oral, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding>90%[4]
MetabolismLiver oxidation and sulfate conjugation
Elimination half-lifeAdults: 24–36 hours[4]
Children: 9.5–24 hours[4]
ExcretionKidney
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 InfoCard100.006.063 Edit this at Wikidata
Chemical and physical data
FormulaC8H7ClN2O2S
Molar mass230.67 g·mol−1
3D model (JSmol)
Melting point330 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) checkY
  • Key:GDLBFKVLRPITMI-UHFFFAOYSA-N checkY
  (verify)

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.[5] This includes islet cell tumors that cannot be removed and leucine sensitivity.[5] It can also be used in refractory cases of sulfonylurea toxicity.[6] It is taken by mouth.[5]

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 (PWS).[3] It was approved for this use in the United States in March 2025.[7]

Common side effects include high blood sugar, fluid retention, low blood platelets, a fast heart rate, increased hair growth, and nausea.[5] Other severe side effects include pulmonary hypertension and heart failure.[5] It is chemically similar to thiazide diuretics.[5] It works by decreasing insulin release from the pancreas and increasing glucose release by the liver.[5]

Diazoxide was approved for medical use in the United States in 1973.[5] It is on the World Health Organization's List of Essential Medicines.[8] It is available as a generic medication.[9]

Medical uses

[edit]

Diazoxide is used as a vasodilator in the treatment of acute hypertension or malignant hypertension.[10]

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)[11] or congenital hyperinsulinism.

Side effects

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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.[6]

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]

Pharmacology

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Pharmacodynamics

[edit]

Diazoxide acts as a ATP-sensitive potassium channel (KATP) opener.[16]

It has been found to act as a positive allosteric modulator of the ionotropic glutamate AMPA and kainate receptors.[17]

Pharmacokinetics

[edit]

The elimination half-life of diazoxide has been reported to be 24 to 36 hours in adults and 9.5 to 24 hours in children.[4]

Research

[edit]

Diazoxide was under development by Lakatos-Topol and Proanagen as a topical solution for the treatment of androgenic alopecia (pattern hair loss) and alopecia areata in the 1980s but was ultimately never marketed.[18][19] It was intended as a competitor and alternative to minoxidil (Rogaine) for such purposes.[18][19] The drug applied topically was found to promote scalp hair growth in balding stump-tailed macaques.[20][21][22][23]

Under the name Vykat XR, diazoxide choline is an approved therapy for Prader-Willi syndrome[3][24][25][26] and is under investigation for monogenic obesity caused by mutations in the SH2B1, PCSK1, or SIM1 genes.[27]

See also

[edit]

References

[edit]
  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 3 "Vykat XR- diazoxide choline tablet, film coated". DailyMed. 26 March 2025. Retrieved 17 April 2025.
  4. 1 2 3 4 "PROGLYCEM (diazoxide) oral suspension label" (PDF). Accessdata.fda.gov. Retrieved 2 August 2026.
  5. 1 2 3 4 5 6 7 8 "Diazoxide Monograph for Professionals". Drugs.com. Retrieved 11 October 2019.
  6. 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.
  7. ↑ "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.
  8. ↑ 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.
  9. ↑ British national formulary: BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 708. ISBN 978-0-85711-338-2.
  10. ↑ 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 icon
  11. ↑ 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 icon
  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 JM, Shoemaker AH, Salehi P, Mejia-Corletto J (June 2026). "Diazoxide choline extended-release (DCCR) use in Prader-Willi syndrome: patient selection, dosing, and management". J Endocr Soc. 10 (6) bvag099. doi:10.1210/jendso/bvag099. PMC 13148164. PMID 42100354.
  17. ↑ 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 icon
  18. 1 2 The Pink Sheet (3 March 1986). "Diazoxide Topical Solution Being Developed As Hair Growth Product". Citeline. Retrieved 27 July 2026. DIAZOXIDE TOPICAL SOLUTION BEING DEVELOPED AS HAIR GROWTH PRODUCT by Lakatos-Topol Research Institute, the company announced in a Feb. 24 press release. Lakatos-Topol said it believes diazoxide is superior to Upjohn's Regaine (minoxidil) as a hair growth stimulant. The firm's release claims that diazoxide "produces a longer and thicker growth of hair" than the Upjohn product. [...] Upjohn has an NDA pending for the topical dosage form for treatment of male pattern baldness and alopecia areata. Lakatos-Topol said it has begun testing the hair growth product outside the U.S. and requested FDA permission to conduct tests in the U.S. An IND has not yet been filed. The firm has also applied for a U.S. patent. Based in Houston, Texas, Lakatos-Topol was formed in July 1985 and went public in January.
  19. 1 2 The Pink Sheet (18 July 1988). "Proanagen's Diazoxide-Based Hair Growth Product Beginning Efficacy". Citeline. Retrieved 27 July 2026. PROANAGEN's DIAZOXIDE-BASED HAIR GROWTH PRODUCT BEGINNING EFFICACY trials as a topically-applied prescription product for the treatment and prevention of hair loss, according to a spokesperson for Pittsburgh-based Proanagen. The company began human studies on the topical formula approximately one year ago, Proanagen said. [...] Large scale efficacy studies will determine if hair growth also occurs when diazoxide is administered topically. Proanagen recently signed a joint development agreement for the product with Schering-Plough and Shiseido. [...] Proanagen was formed in 1987 to develop the diazoxide-based hair loss treatment when Houston-based HRI Inc. (formerly Lakatos-Topol Research Institute) decided not to develop the product.
  20. ↑ Uno H (December 1991). "Quantitative models for the study of hair growth in vivo". Ann N Y Acad Sci. 642 (1): 107–124. Bibcode:1991NYASA.642..107U. doi:10.1111/j.1749-6632.1991.tb24384.x. PMID 1809079. Diazoxide, known as a hypertrichotic agent, also had a stimulatory effect on the bald vellus follicles of macaques." The sequential folliculograms after topical application of diazoxide (5% solution) in the bald scalp are shown in FIGURE 6. A typical folliculogram pattern of the bald scalp showed progressive changes in both folliculograms and quantitative bar graphs of vellus and terminal follicles during treatment.
  21. ↑ Uno H, Kemnitz JW, Cappas A, Adachi K, Sakuma A, Kamoda H (May 1990). "The effects of topical diazoxide on hair follicular growth and physiology of the stumptailed macaque". J Dermatol Sci. 1 (3): 183–194. doi:10.1016/0923-1811(90)90130-6. PMID 2085505.
  22. ↑ Uno H, Kurata S (July 1993). "Chemical agents and peptides affect hair growth". J Invest Dermatol. 101 (1 Suppl): 143S–147S. doi:10.1111/1523-1747.ep12363275. PMID 8326148.
  23. ↑ Buhl AE, Waldon DJ, Conrad SJ, Mulholland MJ, Shull KL, Kubicek MF, et al. (March 1992). "Potassium channel conductance: a mechanism affecting hair growth both in vitro and in vivo". J Invest Dermatol. 98 (3): 315–319. doi:10.1111/1523-1747.ep12499788. PMID 1545141.
  24. ↑ 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.
  25. ↑ 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.
  26. ↑ 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.
  27. ↑ Clinical trial number NCT05532020 for "An Open-Label Study of Diazoxide Choline in Patients With Genetic Obesities" at ClinicalTrials.gov
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