Dydrogesterone is a synthetic progestin. Dydrogesterone alone or in combination with estrogen to endothelial cells results in neutral effects on NO synthesis and on the activity and expression of eNOS. Unlike many other progestational compounds, dydrogesterone produces no increase in temperature and does not inhibit ovulation.
Physicochemical Properties
| Molecular Formula | C21H28O2 |
| Molecular Weight | 312.45 |
| Exact Mass | 312.208 |
| CAS # | 152-62-5 |
| Related CAS # | Levonorgestrel;797-63-7;Dydrogesterone-d6 |
| PubChem CID | 9051 |
| Appearance | White to light yellow solid powder |
| Density | 1.1±0.1 g/cm3 |
| Boiling Point | 462.8±45.0 °C at 760 mmHg |
| Melting Point | 168-173°C |
| Flash Point | 172.2±25.7 °C |
| Vapour Pressure | 0.0±1.1 mmHg at 25°C |
| Index of Refraction | 1.557 |
| LogP | 3.58 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 23 |
| Complexity | 628 |
| Defined Atom Stereocenter Count | 6 |
| SMILES | CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@@H]3[C@H]2C=CC4=CC(=O)CC[C@@]34C)C |
| InChi Key | JGMOKGBVKVMRFX-HQZYFCCVSA-N |
| InChi Code | InChI=1S/C21H28O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h4-5,12,16-19H,6-11H2,1-3H3/t16-,17+,18-,19+,20+,21+/m0/s1 |
| Chemical Name | (8S,9R,10S,13S,14S,17S)-17-acetyl-10,13-dimethyl-1,2,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-one |
| Synonyms | Dydrogesterone Isopregnenone Hydrogesterone Duphaston Hydrogestrone Dufaston Isopregnenone Solvay Brand of Dydrogesterone |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Strong oral progestins like drogesterone are useful for treating a range of gynecological disorders linked to low progesterone levels. Despite having a comparable pharmacological profile and chemical structure to natural progesterone. Even at far smaller dosages, it has an oral effect. Compared to the majority of other synthetic progestins, it has the extra advantage of being free of estrogenic, androgenic, anabolic, corticosteroid, and other negative hormonal effects. In addition, estrogen replacement treatment (HRT) that uses testosterone is approved to prevent the damaging effects of unopposed estrogen on the endometrium in women who have an intact uterus. In addition to being generally well-tolerated and safe, dysgesterone also lacks some of the androgenic adverse effects that are associated with other progestins, like medroxyprogesterone [1]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Rapidly absorbed in the gastrointestinal tract with a bioavailability of 28%. After oral administration of labelled dydrogesterone, on average 63% of the dose is excreted into the urine. Within 72 hours, excretion is complete. After oral administration of dydrogesterone, plasma concentrations of DHD are substantially higher as compared to the parent drug. The AUC and Cmax ratios of DHD to dydrogesterone are in the order of 40 and 25, respectively. Dydrogesterone is rapidly absorbed. The Tmax values of dydrogesterone and DHD vary between 0.5 and 2.5 hours. The dihydrodydrogesterone Caverage is 13 ng/mL, the Cmin is 4.1 ng/mL and the Cmax is 63 ng/mL. The dydrogesterone Caverage is 0.38 ng/mL the Cmin is <0.1 ng/mL and the Cmax is 2.5 ng/mL. Progestins are reportedly distributed into milk. The possible effects of progestins in milk on nursing infants have not been determined. /Progestins General Statement/ Metabolism / Metabolites Metabolism is complete to a 20-dihydrodydrogesterone (DHD) metabolite. In man, dydrogesterone is completely metabolised. The main metabolite of dydrogesterone is 20alpha-dihydrodydrogesterone (DHD) and is present in the urine predominantly as the glucuronic acid conjugate. A common feature of all metabolites characterized is the retention of the 4,6 diene-3-one configuration of the parent compound and the absence of 17alpha-hydroxylation. This explains the absence of estrogenic and androgenic activity. Dydrogesterone is not excreted in urine as pregnanediol, like progesterone. Analysis of endogenous progesterone production based on pregnanediol excretion therefore remains possible. Biological Half-Life Dydrogesterone: 5-7 hours, 20-dihydrodydrogesterone (DHD) metabolite: 14-17 hours Mean terminal half lives of dydrogesterone and DHD vary between 5 to 7 and 14 to 17 hours, respectively. |
| References |
[1]. Dydrogesterone, From Wikipedia, the free encyclopedia. |
| Additional Infomation |
Dydrogesterone is a 3-oxo-Delta(4) steroid and a 20-oxo steroid. It has a role as a progestin. A synthetic progestational hormone with no androgenic or estrogenic properties. Unlike many other progestational compounds, dydrogesterone produces no increase in temperature and does not inhibit ovulation. A synthetic progestational hormone with no androgenic or estrogenic properties. Unlike many other progestational compounds, dydrogesterone produces no increase in temperature and does not inhibit OVULATION. Drug Indication Used to treat irregular duration of cycles and irregular occurrence and duration of periods caused by progesterone deficiency. Also used to prevent natural abortion in patients who have a history of habitual abortions. Mechanism of Action Dydrogesterone is a progestogen that works by regulating the healthy growth and normal shedding of the womb lining by acting on progesterone receptors in the uterus. Dydrogesterone is an orally-active progestagen. The addition of a progestagen greatly reduces the estrogen-induced risk of endometrial hyperplasia and cancer in non-hysterectomised women, by reducing the growth of the endometrium. Progestins cannot be equated as group with progesterone because some are inherently estrogenic, some slightly androgenic, and some purely progestational; correspondingly, their ovulation-inhibiting potentialities may be mediated in somewhat different ways. /Progestins/ The 17-hydroxy or acetoxy compounds, on the other hand, elicit responses more nearly resembling those of progesterone. They have little or no estrogenic or androgenic activity and may produce catabolic and slight diuretic effects. The 19-nor derivatives are more effective in postponing the normal menstrual period. /Progestins/ Accumulating evidence indicates that the neuropeptide substance P (SP) is predominantly involved in neurogenic inflammation and pain perception via its high-affinity neurokinin 1 receptor (NK-1R). Intriguingly, decreased pain sensitivity is found to be associated with high plasma progesterone levels. We hypothesize that progesterone may attenuate nociception and associated inflammatory response via NK-1R-dependent pathways. To address our hypothesis, we incubated splenic lymphocytes from CBA/J female mice with different concentrations of the progesterone derivative dydrogesterone. Subsequently, the expressions of NK-1R and T helper (Th1)-type cytokines were analyzed by flow cytometry. Next, we subcutaneously injected CBA/J mice with 1.25 mg of dydrogesterone in 200-microl sesame oil; control mice were sham-injected. Tail flick test to detect the nociceptive threshold was performed in 30-min intervals upon injection. Lymphocytes were isolated from blood and uterus and analyzed for NK-1R surface expression. Immunohistochemical analyses were performed to investigate the uterine tissue distribution of NK-1R. Dydrogesterone induced a decrease in the percentage of NK-1R+ lymphocytes in vitro and in vivo. Additionally, an increase in Th2-type and a decrease in Th1-type cytokines could be detected in vitro after incubation with dydrogesterone. An increased tail flick latency following dydrogesterone injection supported the concept that decreased expression of the NK-1R on lymphocytes is associated with an increased pain threshold. Taken together, these results clearly reveal a pathway by which dydrogesterone or progesterone respectively modulates the cross talk of the nervous, endocrine and immune systems in inflammation and pain. For more Mechanism of Action (Complete) data for DYDROGESTERONE (6 total), please visit the HSDB record page. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~33.33 mg/mL (~106.67 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.00 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 25.0 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: ≥ 2.5 mg/mL (8.00 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 25.0 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (8.00 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 25.0 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 | 3.2005 mL | 16.0026 mL | 32.0051 mL | |
| 5 mM | 0.6401 mL | 3.2005 mL | 6.4010 mL | |
| 10 mM | 0.3201 mL | 1.6003 mL | 3.2005 mL |