Diazoxide

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Diazoxide
Diazoxide Structural Formula V.1.svg
Systematic (IUPAC) name
7-Chloro-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
Clinical data
Trade names Proglycem
AHFS/Drugs.com Monograph
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Routes of
administration
Oral, intravenous
Legal status
Legal status
Pharmacokinetic data
Protein binding 90%
Metabolism Hepatic oxidation and sulfate conjugation
Biological half-life 21-45 hours
Excretion Renal
Identifiers
CAS Number 364-98-7 YesY
ATC code C02DA01 (WHO) V03AH01 (WHO)
PubChem CID 3019
IUPHAR/BPS 2409
DrugBank DB01119 YesY
ChemSpider 2911 YesY
UNII O5CB12L4FN YesY
KEGG D00294 YesY
ChEBI CHEBI:4495 YesY
ChEMBL CHEMBL181 YesY
Chemical data
Formula C8H7ClN2O2S
Molar mass 230.672 g/mol
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Diazoxide (INN; brand name Proglycem[1]) is a potassium channel activator, which causes local relaxation in smooth muscle by increasing membrane permeability to potassium ions. This switches off voltage-gated calcium ion channels, preventing calcium flux across the sarcolemma and activation of the contractile apparatus.

In the United States, this agent is typically given in hospital.[2]

Uses[edit]

Diazoxide is used as a vasodilator in the treatment of acute hypertension or malignant hypertension.[3]

Diazoxide also inhibits the secretion of insulin from the pancreas, thus it is used to counter hypoglycemia in disease states such as insulinoma (a tumor producing insulin)[4] or congenital hyperinsulinism.

Diazoxide acts as a positive allosteric modulator of the AMPA and kainate receptors, suggesting potential application as a cognitive enhancer.[5]

Side effects[edit]

Diazoxide interferes with insulin release through its action on potassium channels.[6] 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.[7] This mechanism of action is the mirror opposite of that of Sulfonylureas, a class of medications used to increase insulin release in Type 2 Diabetics. Therefore, this medicine is not given to non-insulin dependent diabetic patients.

The Food and Drug Administration published a Safety Announcement in July 2015 highlighting the potential for development of pulmonary hypertension in newborns and infants treated with this drug.[2]

See also[edit]

References[edit]

  1. ^ Diazoxide, drugs.com
  2. ^ a b "FDA Drug Safety Communication: FDA warns about a serious lung condition in infants and newborns treated with Proglycem (diazoxide)" (Press release). Food and Drug Administration. July 16, 2015. Retrieved 2015-07-19. 
  3. ^ 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): 1041–5. doi:10.1097/00004872-199608000-00016. PMID 8884561. Closed access
  4. ^ Huang Q, Bu S, Yu Y, 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 publication - free to read
  5. ^ Randle, John C.R.; Biton, Catherine; Lepagnol, Jean M. (15 November 1993). "Allosteric potentiation by diazoxide of AMPA receptor currents and synaptic potentials". European Journal of Pharmacology. 247 (3): 257–65. doi:10.1016/0922-4106(93)90193-D. PMID 8307099. Closed access
  6. ^ Panten, Uwe; Burgfeld, Johanna; Goerke, Frank; Rennicke, Michael; Schwanstecher, Mathias; Wallasch, Andreas; Zünkler, Bernd J.; Lenzen, Sigurd (1989-04-15). "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. 
  7. ^ Doyle, Máire E.; Egan, Josephine M. (2003-03-01). "Pharmacological Agents That Directly Modulate Insulin Secretion". Pharmacological Reviews. 55 (1): 105–131. doi:10.1124/pr.55.1.7. ISSN 1521-0081. PMID 12615955.