Dydrogesterone

Absorption

Rapidly absorbed in the gastrointestinal tract with a bioavailability of 28%.

Toxicity

No serious or unexpected toxicity has been observed with dydrogesterone. In acute toxicity studies, the LD50 doses in rats exceeded 4,640mg/kg for the oral route.

Description

Dydrogesterone is a synthetic progestogen that has no estrogenic, androgenic, glucocorticoid, or anabolic effects, although it is an agonist of progesterone receptors (EC₅₀ = 12.3 nM) and an antagonist of androgen, mineralocorticoid, and glucocorticoid receptors (IC₅₀s = 28.6, 82.7, and 363 nM, respectively). Dydrogesterone protects against sound stress-induced abortion in mice when administered at a dose of 1.25 mg per animal prior to the stressor on day five of pregnancy. Formulations containing dydrogesterone have been used in hormone replacement therapy, in the treatment of menstrual disorders, and to prevent miscarriage.

Chemical properties

Light Yellow Solid

Originator

Duphaston,Duphar,UK,1961

The Uses of Dydrogesterone

A synthetic progestin largely used in hormone therapy, on the central nervous system by studying two markers of the neuroendocrine function: the neurosteroid allopregnanolone and the opioid .beta.-endorphin. Progestogen.

The Uses of Dydrogesterone

central stimulant, convulsant

Indications

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.

Background

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.

What are the applications of Application

Dydrogesterone is a progestin

What are the applications of Application

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.

Definition

ChEBI: Dydrogesterone is a 3-oxo-Delta(4) steroid and a 20-oxo steroid. It has a role as a progestin.

Manufacturing Process

A solution of 7.5 grams of retroprogesterone in 500 ml of freshly distilled tertiary butyl alcohol was refluxed with 12.75 grams of finely powdered chloranil, while stirring, for 5 hours in a nitrogen atmosphere. After cooling, 2 liters of water were added and extraction was performed three times with 200 ml of methylene dichloride. The combined extracts were then diluted with 1 liter of petroleum ether (40-60°C) washed successively with 100 ml of diluted Na2SO4, four times with 75 ml of 1 N NaOH, and then water to neutral reaction.
By drying this solution on Na2SO4, and evaporating to dryness (last part in vacuo) 3.7 grams of crystalline residue was obtained. This residue was then dissolved in benzene. Filtration in benzene filtered through 35 grams of alumina (according to Brockmann was done and then the alumina was eluted with benzene. Evaporation of the benzene yielded 3.11 grams of crystalline residue. By crystallization with 15 ml of acetone at room temperature (at lower temperatures a by-product crystallized out) 900 mg of crystals, with a melting point of 165°-170°C were obtained. Transfer of the acetone mother liquor into a mixture of ethanol and hexane yielded 1.7 grams of a solid substance with a melting point of 130° to 145°C. This solid was then recrystallized with acetone at room temperature, yielding 600 mg of a solid with a melting point of 166° to 171°C. The two fairly pure fractions (600 mg and 900 mg) yielded, after crystallization with a mixture of acetone and hexane, finally 1.0 gram of 6-dehydroretroprogesterone, melting point 169° to 170°C. From the mother liquors an additional fraction of 0.44 gram with a melting point of 168° to 169°C was obtained.

brand name

Gynorest (Solvay Pharmaceuticals).

Therapeutic Function

Progestin

Pharmacokinetics

Dydrogesterone is an orally active progestogen which acts directly on the uterus, producing a complete secretory endometrium in an estrogen-primed uterus. At therapeutic levels, dydrogesterone has no contraceptive effect as it does not inhibit or interfere with ovulation or the corpus luteum. Furthermore, dydrogesterone is non-androgenic, non-estrogenic, non-corticoid, non-anabolic and is not excreted as pregnanediol. Dydrogesterone helps to regulate the healthy growth and normal shedding of the uterus lining. Therefore, it may be useful in the treatment of menstrual disorders such as absent, irregular or painful menstrual periods, infertility, premenstrual syndrome and endometriosis.

Side Effects

Depression, feeling dizzy, vomiting, liver problems (jaundice (yellow eyes), weakness, stomach pain, generalized discomfort), allergic skin reactions (rashes, itching, redness), weight gain.

Synthesis

Dissolving progesterone, and carrying out photochemical reaction to obtain 9 beta, 10 alpha-pregn-4-ene-3, 20-diketone; mixing the 9 beta, 10 alpha-pregn-4-ene-3, 20-dione, an organic solvent and a benzoquinone oxidant, and carrying out dehydrogenation oxidation reaction to obtain dydrogesterone.

Metabolism

Metabolism is complete to a 20-dihydrodydrogesterone (DHD) metabolite.