| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg |
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| 1g |
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Purity: =99.93%
Diazoxide (also known as Proglycem) is a potassium channel activator used to treat hyperinsulinism. It 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. This agent also inhibits insulin release by interacting with ATP-sensitive potassium channels of pancreatic islet beta-cells.
| Targets |
Potassium channel
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|---|---|
| ln Vitro |
Among its many physiological effects is the reduction of hypertension and hypotension caused by dialezoxide (Sch-6783). Strong antioxidant protection qualities are exhibited by dialzoxide [1]. Diazoxide (Sch-6783) shields NSC-34 neurons, which are a primary cause of neurological damage in the cardiovascular system. In NSC-34 motor neurons, dialzoxide promotes Nrf2 nuclear translocation and guards against endogenous oxidative damage [2].
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| ln Vivo |
Diazoxide (Sch-6783) can reduce brain damage following resuscitation, protect mitochondrial function, block brain cell shutdown, and activate PKC blue by activating mitoKATP channels [3]. Diazoxide (Sch-6783) therapy lowered intraocular pressure (ocular pressure) by 21.5 ± 3.2% in wild-type mice, with an absolute IOP reduction of 3.9 ± 0.6 mm Hg [4].
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| Cell Assay |
NSC-34 cell culture experiments[2]
Motoneuronal NSC-34 Cells were cultured at 37°C and 5% CO2 in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 1% penicillin/streptomycin and 0.04 mM L-glutamine. To differentiate NSC-34 cells to a motoneuronal and glutamate-responsive phenotype, DMEM was replaced by DMEM/Ham’s F12 supplemented with 1% FBS, 1% penicillin/streptomycin and 1% modified Eagle’s medium nonessential amino acids. NSC-34 cells were seeded at low density (3×104 cells/ml) in 24-well plates and were used 72 h after seeding for the toxicity assays. For the treatments, control wells contained the same final concentration of vehicle as the compound-containing wells (0.5% DMSO). Glutamate toxicity assay [2] NSC-34 cells were allowed to differentiate for 8 weeks under reduced serum conditions and then seeded in 24-well plates at a density of 3×104 cells/ml for the following experiment. Glutamate was dissolved in culture medium and added to cultures at concentration of 10 mM for 24 h. Cell treatment with 100 µM diazoxide started 2 h before glutamate exposure. Cell viability was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Hydrogen peroxide exposures [2] To induce oxidative stress, hydrogen peroxide (H2O2) was added to final concentration of 0.2 mM (Stock 30%). NSC-34 cells were exposed to H2O2 for 30 min at 37°C. Then the medium was removed and replaced with fresh medium for 24 h. Cells were treated with 100 µM diazoxide 2 h before H2O2 injury and during 24 h after. Cell viability was measured by the MTT assay. |
| Animal Protocol |
To study Nrf2 activation in diazoxide treated EAE mice, two different administration protocols were performed: in the first one, treatment began on the first day of EAE induction (preventive) whereas the second one started in the chronics phase, when the EAE clinical score was ≥ 1 (appearance of clinical signs, therapeutic). The MOG-immunized mice were administered either 0.8 mg/kg diazoxide (treated group) or diluent (0.3% DMSO in water, vehicle group) for 30 or 15 days by oral gavage, respectively.[2]
Rats: Adult male Sprague-Dawley rats with induced cerebral ischemia (n=10 per group) receive an intraperitoneal injection of 0.1% DMSO (1 mL; vehicle group), diazoxide (10 mg/kg; DZ group), or diazoxide (10 mg/kg) plus 5-hydroxydecanoate (5 mg/kg; DZ + 5-HD group) 30 min after CPR. The control group (sham group, n=5) undergoes sham operation, without cardiac arrest. Mitochondrial respiratory control rate (RCR) is determined. Brain cell apoptosis is assessed using TUNEL staining. Expression of Bcl-2, Bax, and protein kinase C epsilon (PKCε) in the cerebral cortex is determined by Western blotting and immunohistochemistry[3]. Mouse: Diazoxide is prepared by diluting a 100 mM stock solution in 10% polyethoxylated castor oil in PBS. In C57BL/6 wild-type and Kir6.2(−/−) mice, a 5 μL drop of 5 mM diazoxide is topically administered to one eye of each mouse while the fellow control eye received vehicle (DMSO and 10% polyethoxylated castor oil in the same proportion as the treated eye). IOP is measured daily at 1 hour, 4 hours, and 23 hours following treatment. Treatment with diazoxide and vehicle is continued daily for 14 consecutive days[4]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Diazoxide is readily absorbed following oral administration; however, its absorption depends on the dissolution rate of the dosage form. Diazoxide has a bioavailability of 91%. Diazoxide and its metabolites are mainly eliminated through urine. Since diazoxide is extensively protein-bond, it has a slow excretion and a prolonged half-life. In subjects with normal renal function, the urinary excretion rates of diazoxide peak on the first day after oral administration. The apparent volume of distribution of diazoxide in adults with normal renal function is 13 L (21% of body weight), while in children with normal renal function, it is 2 L (33% of body weight). Other sources show that the volume of distribution of diazoxide is 0.21 L/kg. In subjects with normal renal function given 300 mg of diazoxide intravenously, renal clearance was 4 ml/min. Other sources show that the clearance of diazoxide is 0.06 ml/min/kg. Metabolism / Metabolites Diazoxide is metabolized in the liver through oxidation of the 3-methyl group, producing hydroxymethyl (MI) and carboxy (M2) derivatives. The MI derivatives undergo subsequent sulphate conjugation. It is estimated that, in subjects with normal renal function, 54-60% of diazoxide is metabolized. Diazoxide metabolites are inactive and do not contribute to its cardiovascular activity. Additionally, diazoxide metabolites do not displace diazoxide from protein binding sites. Biological Half-Life Following oral administration, the plasma half-life of diazoxide varies from 9.5 to 24 hours in children with normal renal function and from 20 to 72 hours in adults with normal renal function. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation Limited information indicates that maternal doses of oral diazoxide up to 175 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants. If oral diazoxide is required by the mother, it is not a reason to discontinue breastfeeding. Monitoring of the infant’s blood glucose may be advisable, especially during the newborn period. ◉ Effects in Breastfed Infants One infant was partially breastfed (10 to 50% initially, then 80% at 1 month of age) by a mother taking diazoxide orally in dosages of 150 to 175 mg daily for hypoglycemia. At 30 days of age, the infant was developing normally and had experienced no episodes of hypo- or hyperglycemia. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding The protein binding of diazoxide in normal adults can range from 77% to 94%, depending on the administered dose. In patients with renal failure, protein binding ranges between 77% and 87%. This reduction can be related to the lower levels of albumin in patients with renal failure. |
| References |
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| Additional Infomation |
Pharmacodynamics
Diazoxide is a potassium channel activator that enhances cell membrane permeability to potassium ions. By promoting a vasodilatory effect on the smooth muscle in peripheral arterioles, diazoxide lowers blood pressure and peripheral vascular resistance. Diazoxide-induced decreases in blood pressure lead to reflex increases in heart rate and cardiac output. The oral administration of diazoxide increases blood glucose in a dose-dependent manner. In patients with normal renal function, this effect is observed within an hour and lasts no more than eight hours. The hypotensive effects of diazoxide are usually not detected when administered orally. Diazoxide administered intravenously may lead to sodium and water retention, severe hypotension, transient myocardial or cerebral ischaemia and gastrointestinal upsets such as nausea, vomiting and abdominal discomfort. Diazoxide administered orally may cause ketoacidosis and nonketotic hyperosmolar coma, especially in patients with other concurrent conditions. The use of intravenous or oral diazoxide may lead to the development of pulmonary hypertension in infants and neonates. |
| Molecular Formula |
C8H7CLN2O2S
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|---|---|
| Molecular Weight |
230.6714
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| Exact Mass |
229.991
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| Elemental Analysis |
C, 41.65; H, 3.06; Cl, 15.37; N, 12.14; O, 13.87; S, 13.90
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| CAS # |
364-98-7
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| Related CAS # |
Diazoxide-d3;1432063-51-8; 1098065-76-9 (Choline)
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| PubChem CID |
3019
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| Appearance |
White to gray solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
414.8±47.0 °C at 760 mmHg
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| Melting Point |
>310°C
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| Flash Point |
204.6±29.3 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.692
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| LogP |
1.08
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
14
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| Complexity |
360
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
GDLBFKVLRPITMI-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
7-chloro-3-methyl-4H-1$l^{6},2,4-benzothiadiazine 1,1-dioxide
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| Synonyms |
Sch-6783; SRG-95213; Sch6783; SRG95213; Sch 6783; SRG 95213; Eudemine; Hyperstat; Proglycem; Hypertonalum; Proglicem
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 35 mg/mL (~151.73 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (9.02 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (9.02 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.3352 mL | 21.6760 mL | 43.3520 mL | |
| 5 mM | 0.8670 mL | 4.3352 mL | 8.6704 mL | |
| 10 mM | 0.4335 mL | 2.1676 mL | 4.3352 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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