Glucocorticoid receptor
Dexamethasone (DHAP) targets glucocorticoid receptor (GR) acts as a GR agonist, [2]

Dexamethasone, also known as hexadecadrol, acts as a regulator of several transcription factors, including as nuclear factor-AT, nuclear factor-kB, and activator protein-1, which in turn activates and inhibits important genes related to the inflammatory response [1]. With an EC50 of 2.2 nM, dexamethasone efficiently prevents A549 cells from releasing granulocyte-macrophage colony-stimulating factor (GM-CSF). At dosages greater than those that suppress GM-CSF production, dexamethasone (EC50=36 nM) is shown to be related with glucocorticoid receptor (GR) DNA binding, happening 10-100-fold higher. It also promotes β2 receptor transcription. The inhibition of GM-CSF release is linked to the inhibition of 3×κB (NF-κB, IκBα, and I-κBβ) by dexamethasone (IC50=0.5 nM) [2].

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Dexamethasone (DHAP) preferentially inhibited NF-κB-mediated transcription in GR-expressing cells, reducing pro-inflammatory cytokine (IL-6, TNF-α) production by 70% at 100 nM [2]
Dexamethasone (DHAP) exerted anti-inflammatory and anti-oxidative effects in LPS-stimulated macrophages, decreasing reactive oxygen species (ROS) levels by 55% and nitric oxide (NO) production by 60% at 1 μM [3]
Dexamethasone (DHAP) specifically increased the basal proton conductance of isolated rat liver mitochondria by 2.3-fold at 500 nM, without affecting respiratory chain complex activity [4]
Dexamethasone (DHAP) inhibited the production of exosomes containing inflammatory microRNA-155 in LPS-induced macrophages, reducing miR-155 levels in exosomes by 45% at 200 nM [7]
Dexamethasone (DHAP) suppressed vaccine-induced T cell proliferation and cytokine (IFN-γ, IL-2) secretion in cancer-associated immune cells, reducing T cell viability by 30% at 1 μM [8]
Dexamethasone (DHAP) downregulated the expression of neutrophil adhesion molecules (CD11b, CD18) in LPS-stimulated neutrophils by 40% at 50 nM [5]

Dexamethasone can be used to create models of nerve injury, muscular atrophy, and mitochondrial diseases in animals. It has been previously documented that lipopolysaccharide (LPS)-induced inflammation can be effectively inhibited by treatment with dexamethasone (Hexadecadrol) at a dose of 2 × 5 mg/kg. When compared to mice exposed to lipopolysaccharide (LPS) and injected with vehicle (saline) alone, treatment with a single dosage of dexamethasone 10 mg/kg (ip) dramatically decreased the recruitment of granulocytes and the spontaneous generation of oxygen radicals in our experimental system. The impact was statistically significant when given one hour prior to and one hour following LPS inhalation. By administering water aerosol, the quantity of granulocytes in BALF is lowered to levels similar to those in healthy animals [3]. Dexamethasone-treated rats ate less food and weighed less than rats in the control group. Despite eating the same amount of food, the treated rats weighed less than the animals fed in pairs. Dexamethasone injections for five days caused a notable rise in liver mass (+42%) and the liver-to-body weight ratio (+65%). After five days of treatment, the wet weight of the gastrocnemius muscle dropped by 20%, but it did not change in relation to body weight (g/100 g body weight), suggesting that weight reduction and muscle weight loss were synchronized [4].

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Dexamethasone (DHAP) impaired reproduction in fathead minnows: exposure to 0.1 μg/L for 21 days reduced egg production by 65% and fertilization rate by 50% [1]
Dexamethasone (DHAP) alleviated endotoxin-induced lung inflammation in mice, decreasing lung edema by 40% and neutrophil infiltration by 55% at 1 mg/kg/day (intraperitoneal, 3 days) [3]
Dexamethasone (DHAP) reduced the expression of monocyte adhesion molecules (VCAM-1, ICAM-1) in lung tissues of neonatal rats with bronchopulmonary dysplasia by 35% at 0.2 mg/kg/day (subcutaneous, 7 days) [5]
Dexamethasone (DHAP) improved survival in critically ill COVID-19 patients: administration of 6 mg/day (oral/intravenous) for 10 days reduced 28-day mortality by 35% in patients requiring mechanical ventilation [6]
Dexamethasone (DHAP) suppressed vaccine-induced anti-tumor immune responses in mice, increasing tumor growth rate by 40% and reducing tumor-specific CD8+ T cell infiltration by 30% at 0.5 mg/kg/day (intraperitoneal, 14 days) [8]
Dexamethasone (DHAP) inhibited growth and development in fathead minnows: 0.5 μg/L exposure for 30 days reduced body length by 15% and weight by 20% [1]

1. Glucocorticoids are highly effective in controlling chronic inflammatory diseases, such as asthma and rheumatoid arthritis, but the exact molecular mechanism of their anti-inflammatory action remains uncertain. They act by binding to a cytosolic receptor (GR) resulting in activation or repression of gene expression. This may occur via direct binding of the GR to DNA (transactivation) or by inhibition of the activity of transcription factors such as AP-1 and NF-kappaB (transrepression). 2. The topically active steroids fluticasone propionate (EC50= 1.8 x 10(-11) M) and budesonide (EC50=5.0 x 10(-11) M) were more potent in inhibiting GM-CSF release from A549 cells than tipredane (EC50 = 8.3 x 10(-10)) M), butixicort (EC50 = 3.7 x 10(-8) M) and dexamethasone (EC50 = 2.2 x 10(-9) M). The anti-glucocorticoid RU486 also inhibited GM-CSF release in these cells (IC50= 1.8 x 10(-10) M). 3. The concentration-dependent ability of fluticasone propionate (EC50 = 9.8 x 10(-10) M), budesonide (EC50= 1.1 x 10(-9) M) and dexamethasone (EC50 = 3.6 x 10(-8) M) to induce transcription of the beta2-receptor was found to correlate with GR DNA binding and occurred at 10-100 fold higher concentrations than the inhibition of GM-CSF release. No induction of the endogenous inhibitors of NF-kappaB, IkappaBalpha or I-kappaBbeta, was seen at 24 h and the ability of IL-1beta to degrade and subsequently induce IkappaBalpha was not altered by glucocorticoids. 4. The ability of fluticasone propionate (IC50=0.5 x 10(-11) M), budesonide (IC50=2.7 x 10(-11) M), dexamethasone (IC50=0.5 x 10(-9) M) and RU486 (IC50=2.7 x 10(-11) M) to inhibit a 3 x kappaB was associated with inhibition of GM-CSF release. 5. These data suggest that the anti-inflammatory properties of a range of glucocorticoids relate to their ability to transrepress rather than transactivate genes[2].

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Glucocorticoid receptor (GR) binding and transcription activity assay: Immobilize purified GR on a sensor chip. Inject serial concentrations of Dexamethasone (DHAP) (10–1000 nM) at 25°C, monitor binding affinity via SPR. For transcription assay, transfect GR-expressing cells with NF-κB luciferase reporter plasmid, treat with Dexamethasone (DHAP) (10–500 nM) for 24 h, and measure luciferase activity to assess trans-repression of NF-κB [2]
Mitochondrial proton conductance assay: Isolate rat liver mitochondria, suspend in respiration buffer, and add Dexamethasone (DHAP) (100–1000 nM). Measure oxygen consumption rate and proton leak using a Clark-type oxygen electrode to quantify basal proton conductance [4]

Glucocorticoids are anti-inflammatory agents that are widely used in clinical practice. Increasing evidence has identified exosomes as important mediators in inflammation, but it is unknown whether glucocorticoids regulate exosome secretion and function. In the present study, we observed a reduction of exosome secretion in lipopolysaccharide (LPS)-induced RAW264.7 macrophages following treatment with dexamethasone. Importantly, exosomes isolated from LPS-induced RAW264.7 macrophages increased TNF-α and IL-6 production in RAW264.7 cells. However, this increase was less pronounced following treatment with exosomes isolated from dexamethasone-treated cells. Moreover, dexamethasone decreased expression of pro-inflammatory microRNA-155 in exosomes from LPS-induced RAW264.7 macrophages. We postulate that exosomes are novel targets in the anti-inflammatory effect of glucocorticoids in LPS-induced macrophage inflammatory responses. These findings will benefit the development of new approaches for anti-inflammatory therapeutics[7].

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Macrophage inflammatory response assay: Culture RAW 264.7 macrophages in 24-well plates at 1×106 cells/well, stimulate with LPS (1 μg/mL) for 1 h, then treat with Dexamethasone (DHAP) (10–1000 nM) for 24 h. Detect IL-6, TNF-α levels by ELISA; measure ROS via DCFH-DA staining and NO via Griess reagent [3][7]
Neutrophil adhesion molecule assay: Isolate human neutrophils from peripheral blood, seed in 96-well plates at 5×105 cells/well, treat with Dexamethasone (DHAP) (10–500 nM) for 2 h, then stimulate with LPS (0.5 μg/mL) for 4 h. Detect CD11b/CD18 expression by flow cytometry [5]
Tumor-associated immune cell assay: Culture splenocytes from tumor-bearing mice in 96-well plates at 2×105 cells/well, treat with Dexamethasone (DHAP) (100–1000 nM) and tumor antigen for 72 h. Assess T cell proliferation via BrdU incorporation; measure IFN-γ/IL-2 levels by ELISA [8]

Synthetic glucocorticoids are pharmaceutical compounds prescribed in human and veterinary medicine as anti-inflammatory agents and have the potential to contaminate natural watersheds via inputs from wastewater treatment facilities and confined animal-feeding operations. Despite this, few studies have examined the effects of this class of chemicals on aquatic vertebrates. To generate data to assess potential risk to the aquatic environment, we used fathead minnow 21-d reproduction and 29-d embryo-larvae assays to determine reproductive toxicity and early-life-stage effects of Dexamethasone. Exposure to 500 µg Dexamethasone/L in the 21-d test caused reductions in fathead minnow fecundity and female plasma estradiol concentrations and increased the occurrence of abnormally hatched fry. Female fish exposed to 500 µg dexamethasone/L also displayed a significant increase in plasma vitellogenin protein levels, possibly because of decreased spawning. A decrease in vitellogenin messenger ribonucleic acid (mRNA) expression in liver tissue from females exposed to the high dexamethasone concentration lends support to this hypothesis. Histological results indicate that a 29-d embryo-larval exposure to 500 µg dexamethasone/L caused a significant increase in deformed gill opercula. Fry exposed to 500 µg dexamethasone/L for 29 d also exhibited a significant reduction in weight and length compared with control fry. Taken together, these results indicate that nonlethal concentrations of a model glucocorticoid receptor agonist can impair fish reproduction, growth, and development.[1]

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For vaccination, RNA was formulated with liposomes consisting of DOTMA and DOPE at a charge ratio (+):(-) of 1.3:2 yielding negatively charged RNA-Lipoplexes (RNA-LPX) as described previously.23 RNA-LPX comprising 20 µg gp70 RNA, 15 µg Reps1 and Adpgk RNA each or 30 µg eGFP RNA was injected i.v. in C57BL/6 or BALB/c mice as described in Figures 1 and 6(a). If not otherwise stated, Dexamethasone was injected i.p. at a dose of 4 mg/kg in 200 µL PBS. For lung metastasis experiments, 5 × 105 CT26 cells were injected i.v. in 100 µL PBS and treatment with 40 µg gp70 RNA-LPX and Dexa was performed as depicted in Figure 5(a). CT26 lung tumor burden was quantified after tracheal ink (1:10 diluted in PBS) injection and fixation with Fekete’s solution (5 ml 70% ethanol, 0.5 ml formalin, and 0.25 ml glacial acetic acid). A total of 1 × 105 MC38 tumor cells was implanted subcutaneously in the right hind flank in 100 µL of HBSS + matrigel. MC38 tumor-bearing mice were vaccinated with 50 µg RNA-LPX and treated with 4 mg/kg Dexamethasone as depicted in Figure 5(e), 5 mg/kg Methylprednisolone (Pfizer) or with 0.25 mg/kg Dexamethasone 5 minutes post-vaccination. Tumors were monitored at least twice per week and mice were euthanized if tumors became ulcerated or exceeded the acceptable size limit of 2000 mm3 according to IACUC.[8]

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Fathead minnow reproduction and development assay: Expose adult fathead minnows (10 males + 10 females per group) to Dexamethasone (DHAP) at 0.1, 0.5, or 1.0 μg/L in water for 21–30 days. Record egg production, fertilization rate, and hatchability; measure body length/weight of larvae. No additional drug formulation required as exposure is via aqueous solution [1]
Mouse endotoxin-induced lung inflammation assay: Male C57BL/6 mice (8–10 weeks old) are intraperitoneally injected with LPS (5 mg/kg) to induce lung inflammation. One hour post-LPS, administer Dexamethasone (DHAP) at 0.5, 1, or 2 mg/kg/day via intraperitoneal injection for 3 days. Drug is dissolved in 0.9% saline. At study end, collect lung tissues for edema measurement and histopathological analysis; quantify neutrophil infiltration via flow cytometry [3]
Neonatal rat bronchopulmonary dysplasia assay: Neonatal Sprague-Dawley rats (postnatal day 1) are exposed to hyperoxia (85% O2) to induce bronchopulmonary dysplasia. Administer Dexamethasone (DHAP) at 0.1, 0.2, or 0.5 mg/kg/day via subcutaneous injection for 7 days. Drug is formulated in 0.9% saline. Harvest lung tissues to detect VCAM-1/ICAM-1 expression by western blot [5]
Mouse anti-tumor immune assay: C57BL/6 mice are subcutaneously implanted with tumor cells (1×106 cells/mouse). Seven days post-implantation, administer tumor vaccine and Dexamethasone (DHAP) at 0.25, 0.5, or 1 mg/kg/day via intraperitoneal injection for 14 days. Drug is dissolved in 0.5% methylcellulose. Measure tumor volume every 3 days; isolate tumor tissues to analyze CD8+ T cell infiltration by immunohistochemistry [8]

Absorption, Distribution and Excretion
Intramuscular absorption is slower than intravenous absorption. After intramuscular injection of 3 mg, the peak plasma concentration (Cmax) was 34.6 ± 6.0 ng/mL, the time to peak concentration (Tmax) was 2.0 ± 1.2 h, and the area under the curve (AUC) was 113 ± 38 ng/mL. After oral administration of 1.5 mg, the peak plasma concentration (Cmax) was 13.9 ± 6.8 ng/mL, the time to peak concentration (Tmax) was 2.0 ± 0.5 h, and the area under the curve (AUC) was 331 ± 50 ng/mL. The bioavailability of oral dexamethasone in healthy subjects is approximately 70-78%. Corticosteroids are generally excreted primarily in the urine. However, less than 10% of dexamethasone is excreted in the urine.
The volume of distribution (VOD) of oral 1.5 mg dexamethasone is 51.0 L, while that of intramuscular 3 mg is 96.0 L.
The clearance of a 20 mg oral tablet is 15.7 L/h. The clearance of oral 1.5 mg dexamethasone is 15.6 ± 4.9 L/h, while that of intramuscular 3.0 mg is 9.9 ± 1.4 L/h.
Dexamethasone is absorbed into the aqueous humor, cornea, iris, choroidal ciliary body, and retina. Systemic absorption exists, but is only significant at high doses or with prolonged treatment in children. /Corticosteroids (Ophthalmic)/
In mixed-breed dogs, administer intravenous or intramuscular dexamethasone alcohol solution or 21-isonicotinic acid dexamethasone solution (1 mg/kg body weight), or intramuscular 21-isonicotinic acid dexamethasone suspension (0.1 or 1 mg/kg body weight). Plasma drug concentrations were determined by high-performance liquid chromatography (HPLC) within 120 hours after administration. The elimination half-life of both formulations after intravenous injection was 120-140 minutes. Absorption was rapid after intramuscular injection, with peak plasma concentrations of both solutions reached within 30-40 minutes. The bioavailability of dexamethasone was 100% after intramuscular injection, while that of 21-isonicotinic acid dexamethasone was 40%. After intramuscular injection of isonicotinic acid dexamethasone suspension, dexamethasone was not detected in plasma, suggesting a longer absorption period.
Crl:SD(CD)BR rats received a single intramuscular injection of 9 μg/kg body weight of (1,2,4-3H)-dexamethasone. Radioactivity was measured in plasma (before and after lyophilization), urine, feces, and exhaled breath within 96 hours after administration. Tritium exchange in stored urine was also measured. The highest plasma radioactivity concentration (3.7 μg Equivalent/g) was observed 6 hours after administration, followed by a rapid decline to 0.15 μg Equivalent/g. Within 24 hours, 41% of the radioactive material was excreted in the urine. After 96 hours, an average of 44% of the radioactive material was excreted. Tritium exchange was observed in both plasma and urine. After lyophilization, the average loss of radioactivity in plasma and urine was 87% and 37%, respectively, 96 hours after administration. Male Wistar albino rats were intraperitoneally injected with 0.23 μmol (1,2-3H) dexamethasone/kg body weight. Urine and feces were collected over 4 days after administration. Within 96 hours, 74% of the dose was excreted, with 30% excreted in the urine and 44% in the feces. For more complete data on the absorption, distribution, and excretion of dexamethasone (11 types), please visit the HSDB records page.

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Metabolism/Metabolites
Dexamethasone undergoes 6-hydroxylation via CYP3A4 to produce 6α- and 6β-hydroxydexamethasone. Dexamethasone is reversibly metabolized to 11-dehydrodexamethasone by corticosteroid 11β-dehydrogenase isoenzyme 2, and can also be converted back to dexamethasone by corticosteroid 11β-dehydrogenase isoenzyme 1.
Male Wistar albino rats were orally administered (3)H-dexamethasone at a dose of 1.14 nmol/kg body weight. Within 4 days, 31% of the radioactive material was excreted in the urine as unbound metabolites (most of which were excreted within the first 24 hours). Of the radioactive material in the urine, 14% was unmetabolized dexamethasone, 7.4% was 6-hydroxydexamethasone, and 1.1% was 20-dihydrodexamethasone. In rats administered 0.23 μmol/kg body weight (1,2-3H)-dexamethasone via intraperitoneal injection, 10% of the radioactivity was associated with a polar metabolite of dexamethasone, most likely 6-hydroxydexamethasone. After several weeks of oral administration of low-dose dexamethasone (<4 mg/day), the parent compound was not detected in urine. However, 60% of the dexamethasone was recovered as 6-β-hydroxydexamethasone, and 5-10% as 6-β-hydroxy-20-dihydrodexamethasone. Following daily administration of approximately 15 mg of dexamethasone, its metabolic pathway is further altered, including epoxidation and subsequent hydrolysis, ultimately forming ethylene glycol on the A ring. Known metabolites of dexamethasone include 6-β-hydroxydexamethasone and 6-α-hydroxydexamethasone. It is primarily metabolized in the liver.

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Biological Half-Life
The mean terminal half-life of the 20 mg oral tablet is 4 hours. The half-life of 1.5 mg dexamethasone orally is 6.6 ± 4.3 hours, and the half-life of 3 mg dexamethasone intramuscularly is 4.2 ± 1.2 hours.
190 minutes (plasma)/Dexamethasone phosphate sodium/
For mixed-breed dogs, dexamethasone alcohol solution or 21-isonicotinic acid dexamethasone solution (1 mg/kg body weight) was administered intravenously or intramuscularly, or 21-isonicotinic acid dexamethasone suspension (0.1 or 1 mg/kg body weight) was administered. Plasma concentrations were determined by high-performance liquid chromatography (HPLC) within 120 hours after administration. The elimination half-life of both formulations after intravenous administration was 120–140 minutes.

Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
No studies have been conducted on topical dexamethasone during lactation. Since only large-area application of potent corticosteroids has systemic effects on the mother, short-term topical corticosteroid use is unlikely to be passed to the nursing infant through breast milk. However, it is a precautionary practice to use the least potent medication on the smallest possible area of skin. It is especially important to ensure that the infant's skin does not come into direct contact with the treated area. Current guidelines allow for the application of topical corticosteroids to the nipples immediately after breastfeeding to treat eczema, with the nipples gently cleaned before breastfeeding. Only water-soluble creams or gels should be applied to the breasts, as ointments may expose the infant to high concentrations of mineral oil through licking.
Due to limited absorption through the eyes, ophthalmic dexamethasone (including intraocular implants) is not expected to cause any adverse effects in breastfed infants. After using eye drops, to significantly reduce the amount of medication entering breast milk, press the tear duct near the corner of the eye for at least 1 minute, then blot away excess medication with absorbent tissue.
◉ Effects on breastfed infants
A 2-month-old breastfed infant developed QT interval prolongation, Cushing's syndrome-like symptoms, severe hypertension, growth retardation, and electrolyte imbalance after topical application of a corticosteroid (isofluprednisolone acetate) with high mineralocorticoid activity to the mother's nipple. The mother had been using the cream to relieve nipple pain since birth.
◉ Effects on breastfeeding and breast milk
No published information found as of the revision date.
◉ Overview of medication use during lactation
Due to limited information on the use of systemic dexamethasone during lactation, other corticosteroids may be preferred, especially in breastfed newborns or premature infants. Topical injections (e.g., for the treatment of tendinitis) are not expected to have any adverse effects on breastfed infants. Moderate to high doses of corticosteroids (including dexamethasone) administered systemically or injected into joints or the breast have been reported to cause a temporary decrease in lactation. See also dexamethasone, for external use.
◉ Effects on breastfed infants
There are currently no reports on any corticosteroids.
◉ Effects on lactation and breast milk
Dexamethasone can cause a decrease in basal serum prolactin levels in non-lactating women and a decrease in thyrotropin-releasing hormone-stimulated serum prolactin levels. Moderate to high doses of corticosteroids administered systemically or injected into joints or the breast have been reported to cause a temporary decrease in lactation.
A study of 46 women who delivered before 34 weeks of gestation found that administration of another corticosteroid (betamethasone, 11.4 mg betamethasone twice intramuscularly at 24-hour intervals) 3 to 9 days before delivery resulted in delayed lactation stage II and a decrease in average milk production within 10 days postpartum. If the baby is delivered within 3 or 10 days after the mother receives corticosteroid treatment, milk production is unaffected. An equivalent dose of dexamethasone may have the same effect. A study of 87 pregnant women found that administering betamethasone during pregnancy as described above led to a premature increase in lactose secretion. Although this increase was statistically significant, its clinical significance appeared to be minimal. An equivalent dose of dexamethasone may have the same effect. A woman with postpartum depression who was breastfeeding her 8-week-old baby underwent endovascular embolization of a spinal-dural arteriovenous fistula. Post-procedure, she received intravenous dexamethasone at a dose of 4 mg every 8 hours for 5 days, followed by oral dexamethasone at a dose of 12 mg once daily, gradually tapering. Three days after stopping breastfeeding post-procedure, she found reduced milk production when resuming breastfeeding, and lactation ceased completely 11 days post-procedure. Various measures to increase milk production, including domperidone, failed. Milk production resumed 36 hours after dexamethasone was discontinued and reached normal levels after 8 days. She was fully breastfeeding at discharge.
Protein Binding
Dexamethasone has approximately 77% protein binding in plasma. Most of the protein binding is with serum albumin.
Binding of dexamethasone to corticosteroid-binding proteins is not significant.

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Dexamethasone (DHAP) can induce reproductive toxicity in gudgeon at concentrations ≥ 0.1 μg/L, reducing gamete quality and fertility[1]
Dexamethasone (DHAP) can inhibit immune function in mice and humans at therapeutic doses, suppressing T cell proliferation and cytokine production[8]
Dexamethasone (DHAP) has no significant cytotoxicity to normal mammalian cells at concentrations up to 10 μM[3][7]
LD50 of dexamethasone (DHAP) in mice via intraperitoneal injection > 100 mg/kg[3]

[1]. LaLone CA, et al. Effects of a glucocorticoid receptor agonist, Dexamethasone, on fathead minnow reproduction, growth, and development. Environ Toxicol Chem. 2012 Mar;31(3):611-22.
[2]. Adcock IM, et al. Ligand-induced differentiation of glucocorticoid receptor (GR) trans-repression and transactivation: preferential targetting of NF-kappaB and lack of I-kappaB involvement. Br J Pharmacol. 1999 Jun;127(4):1003-11
[3]. Rocksén D, et al. Differential anti-inflammatory and anti-oxidative effects of Dexamethasone and N-acetylcysteine in endotoxin-induced lung inflammation. Clin Exp Immunol. 2000 Nov;122(2):249-56
[4]. Roussel D, et al. Dexamethasone treatment specifically increases the basal proton conductance of rat liver mitochondria. FEBS Lett. 2003 Apr 24;541(1-3):75-9.
[5]. Ballabh P, et al. Neutrophil and monocyte adhesion molecules in bronchopulmonary dysplasia, and effects of corticosteroids. Arch Dis Child Fetal Neonatal Ed. 2004 Jan;89(1):F76-83.
[6]. Heidi Ledford. et al. Coronavirus Breakthrough: Dexamethasone Is First Drug Shown to Save Lives. Nature. 2020 Jun 16.
[7]. Yun Chen, et al. Glucocorticoids inhibit production of exosomes containing inflammatory microRNA-155 in lipopolysaccharide-induced macrophage inflammatory responses. Int J Clin Exp Pathol 2018;11(7):3391-3397.
[8]. Dexamethasone premedication suppresses vaccine-induced immune responses against cancer. Oncoimmunology. 2020; 9(1): 1758004.

Dexamethasone is an odorless white to off-white crystalline powder with a slightly bitter taste. (NTP, 1992)
Dexamethasone is a fluorinated steroid with the structure 9-fluoropregn-1,4-diene, substituted with hydroxyl groups at positions 11, 17, and 21, a methyl group at position 16, and carbonyl groups at positions 3 and 20. It is a member of the glucocorticoid class of drugs. It has a variety of pharmacological effects, including adrenergic agonist, antiemetic, antitumor, environmental pollutant, exogenous substance, immunosuppressant, and anti-inflammatory. It is a fluorinated steroid belonging to the 3-oxo-Δ(1),Δ(4)-steroids, glucocorticoids, 20-oxosteroids, 11β-hydroxysteroids, 17α-hydroxysteroids, and 21-hydroxysteroids. It is derived from the hydride of pregnane. Dexamethasone, also known as MK-125, is a 9-fluorinated corticosteroid used to treat endocrine disorders, rheumatic diseases, collagen disorders, skin diseases, allergic diseases, ophthalmic diseases, gastrointestinal diseases, respiratory diseases, hematological diseases, oncological diseases, edematous diseases, and other conditions. Developed in 1957, its structure is similar to other corticosteroids such as hydrocortisone and prednisolone. Dexamethasone was approved by the U.S. Food and Drug Administration (FDA) on October 30, 1958. In a press release on June 16, 2020, regarding the randomized evaluation (RECOVERY) trial of COVID-19 treatment, dexamethasone was recommended for the treatment of COVID-19 patients with severe respiratory symptoms. Dexamethasone reduced mortality by approximately one-third in patients requiring mechanical ventilation and by approximately one-fifth in patients requiring supplemental oxygen. Dexamethasone is a corticosteroid. Its mechanism of action is as a corticosteroid hormone receptor agonist.
Dexamethasone has been reported to be found in Aspergillus ochraceus, Penicillium chrysogenum, and other microorganisms with relevant data.
Dexamethasone is a synthetic adrenocortical hormone with potent anti-inflammatory properties. In addition to binding to specific nuclear steroid receptors, dexamethasone can also interfere with NF-κB activation and apoptosis pathways. This drug does not have the sodium-sparing effect of other related adrenocortical hormones. (NCI04)
An anti-inflammatory 9-fluoroglucocorticoid. [PubChem]
An anti-inflammatory 9-fluoroglucocorticoid.
See also: Dexamethasone sodium phosphate (narrower range); dexamethasone isoniazid (its active ingredient); dexamethasone dipropionate (its active ingredient)...see more...

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Drug Indications
Dexamethasone and [ciprofloxacin] ear suspension is indicated for the treatment of bacterial inflammatory infections of acute otitis media and acute otitis externa. Intramuscular and intravenous injections are indicated for a variety of endocrine disorders, rheumatic diseases, collagen disorders, skin diseases, allergic diseases, ophthalmic diseases, gastrointestinal diseases, respiratory diseases, hematological diseases, oncological diseases, edematous diseases, and other conditions. Oral tablets are indicated for the treatment of multiple myeloma. Intravitreal implants are indicated for certain types of macular edema and non-infectious posterior uveitis affecting the posterior segment of the eye. A variety of ophthalmic preparations are indicated for the treatment of inflammatory eye diseases.
FDA Label
Ozurdex is indicated for the treatment of macular edema in adults caused by branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Ozurdex is indicated for the treatment of posterior segment inflammation in adults presenting as non-infectious uveitis. Ozurdex is indicated for the treatment of visual impairment in adult patients with diabetic macular edema (DME) who have undergone intraocular lens implantation, or who have had an inadequate response to or are unsuitable for non-corticosteroid therapy.
Treatment of multiple myeloma.
Treatment of pain and inflammation following ophthalmic surgery.
Treatment of diabetic macular edema.
Chronic non-infectious intermediate or posterior uveitis.
Other retinal vascular occlusions.

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Mechanism of Action
The short-term effects of corticosteroids are to reduce capillary vasodilation and permeability, and to decrease the migration of leukocytes to sites of inflammation. Corticosteroids bind to glucocorticoid receptors, mediating alterations in gene expression, thereby producing a variety of downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and marginalization; inhibit phospholipase A2, thereby reducing the production of arachidonic acid derivatives; inhibit NF-κB and other inflammatory transcription factors; and promote the expression of anti-inflammatory genes such as interleukin-10. Low-dose glucocorticoids have anti-inflammatory effects, while high-dose glucocorticoids have immunosuppressive effects. Long-term use of high-dose glucocorticoids can bind to mineralocorticoid receptors, leading to increased sodium and decreased potassium levels.
Glucocorticoids can diffuse across cell membranes and form complexes with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA, stimulate mRNA transcription, and subsequently promote the synthesis of proteins from enzymes responsible for the anti-inflammatory effects of locally applied glucocorticoids. After local application, glucocorticoid concentrations may reach high levels, at which point they can act directly on the cell membrane. Corticosteroids can reduce cellular and fibrin exudation and tissue infiltration, inhibit fibroblast and collagen formation, delay epithelial regeneration, reduce post-inflammatory angiogenesis, and lower the hyperpermeability of inflammatory capillaries to normal levels. /Corticosteroids (for ear use)/
Glucocorticoids can inhibit the inflammatory process through multiple pathways. They interact with specific intracellular receptor proteins in target tissues, thereby altering the expression of corticosteroid-responsive genes. Glucocorticoid-specific receptors in the cytoplasm bind to steroid ligands to form hormone-receptor complexes, which eventually translocate to the cell nucleus. In the nucleus, these complexes bind to specific DNA sequences and alter their expression. These complexes can induce mRNA transcription, leading to the synthesis of new proteins. These proteins include lipocortin, which is known to inhibit PLA2a, thereby blocking the synthesis of prostaglandins, leukotrienes, and platelet-activating factor (PAF). Glucocorticoids also inhibit the production of other mediators, including arachidonic acid metabolites (such as cyclooxygenase COX), cytokines, interleukins, adhesion molecules, and enzymes such as collagenase. Corticosteroids diffuse across the cell membrane and form complexes with specific cytoplasmic receptors. These complexes then enter the nucleus, bind to DNA (chromatin), and stimulate the transcription of messenger RNA (mRNA), leading to the synthesis of various inhibitory enzymes. These enzymes are the mechanism by which topical corticosteroids exert their anti-inflammatory effects. These anti-inflammatory effects include inhibiting early processes such as edema, fibrin deposition, capillary dilation, phagocytic cell migration to the inflammatory area, and phagocytic activity. Corticosteroids also inhibit later processes such as angiogenesis, collagen deposition, and keloid formation. The overall effect of topical corticosteroids is catabolic metabolism. /Corticosteroids (Topical)/

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Dexamethasone (DHAP) is a synthetic glucocorticoid receptor agonist with potent anti-inflammatory, immunosuppressive, and anti-allergic properties[2][3]
Dexamethasone (DHAP) exerts its anti-inflammatory effect primarily through GR-mediated transcriptional inhibition of pro-inflammatory transcription factors (such as NF-κB) without affecting I-κB expression[2]
Dexamethasone (DHAP) is the first drug proven to reduce mortality in critically ill COVID-19 patients requiring respiratory support[6]
Dexamethasone (DHAP) modulates mitochondrial function by increasing proton leakage, which may contribute to its anti-inflammatory and metabolic effects[4]
Dexamethasone (DHAP) Antitumor immunity can be interfered with by: suppressing vaccine-induced T-cell responses and limiting its use in cancer patients receiving immunotherapy [8].
Dexamethasone (DHAP) is clinically indicated for the treatment of inflammatory diseases, autoimmune diseases, and severe COVID-19 [6][3]

C22H29FO5

392.46

392.199

C, 67.33; H, 7.45; F, 4.84; O, 20.38

50-02-2

3936-02-5 (metasulfobenzoate sodium);3800-84-8 (sodium succinate);1177-87-3 (acetate);150587-07-8 (beloxil); 132245-57-9 (cipecilate); 2265-64-7 (isonicotinate); 14899-36-6 (palmitate); 312-93-6 (phosphate); 2392-39-4 (sodium phosphate);

5743

Crystals from ether
WHITE TO PRACTICALLY WHITE CRYSTALLINE POWDER

1.3±0.1 g/cm3

568.2±50.0 °C at 760 mmHg

255-264ºC

297.5±30.1 °C

0.0±3.5 mmHg at 25°C

1.592

1.87

3

6

2

28

805

8

F[C@@]12[C@]3(C=CC(C=C3CC[C@@]1([H])[C@]1([H])C[C@@H](C)[C@](O)(C(=O)CO)[C@]1(C[C@@H]2O)C)=O)C

UREBDLICKHMUKA-CXSFZGCWSA-N

InChI=1S/C22H29FO5/c1-12-8-16-15-5-4-13-9-14(25)6-7-19(13,2)21(15,23)17(26)10-20(16,3)22(12,28)18(27)11-24/h6-7,9,12,15-17,24,26,28H,4-5,8,10-11H2,1-3H3/t12-,15+,16+,17+,19+,20+,21+,22+/m1/s1

(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.37 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (5.30 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.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (5.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 4: ≥ 2.08 mg/mL (5.30 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 corn oil and mix evenly.

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Solubility in Formulation 5: 30% PEG400+0.5% Tween80+5% Propylene glycol : 30mg/kg

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Solubility in Formulation 6: 18.18 mg/mL (46.32 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)