Мы используем файлы cookie.
Продолжая использовать сайт, вы даете свое согласие на работу с этими файлами.
Abandoned drugs
Estradiol dienantate
Другие языки:

    Estradiol dienantate

    Подписчиков: 0, рейтинг: 0
    Not to be confused with Estradiol enanthate.
    Estradiol dienantate
    Estradiol dienanthate.svg
    Estradiol dienanthate molecule ball.png
    Clinical data
    Trade names Climacteron, Amenose, Lactimex, Lactostat (all combinations)
    Other names Estradiol dienantate; EDE; EDEn; E2-EDN; Estradiol diheptanoate; Estra-1,3,5(10)-triene-3,17β-diol 3,17β-diheptanoate
    Routes of
    administration    		 Intramuscular injection
    Drug class Estrogen; Estrogen ester
    Identifiers
    • [(8R,9S,13S,14S,17S)-3-heptanoyloxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] heptanoate
    CAS Number
    PubChem CID
    DrugBank
    ChemSpider
    UNII
    ECHA InfoCard 100.028.903
    Chemical and physical data
    Formula C32H48O4
    Molar mass 496.732 g·mol−1
    3D model (JSmol)
    • CCCCCCC(=O)O[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=C3C=CC(=C4)OC(=O)CCCCCC)C
    • InChI=1S/C32H48O4/c1-4-6-8-10-12-30(33)35-24-15-17-25-23(22-24)14-16-27-26(25)20-21-32(3)28(27)18-19-29(32)36-31(34)13-11-9-7-5-2/h15,17,22,26-29H,4-14,16,18-21H2,1-3H3/t26-,27-,28+,29+,32+/m1/s1
    • Key:OVAHZPTYWMWNKO-CAHAWPIUSA-N

    Estradiol dienanthate (EDE), sold under the brand names Climacteron among others, is a long-acting estrogen medication which was previously used in menopausal hormone therapy for women and to suppress lactation in women. It was formulated in combination with estradiol benzoate (EB), a short-acting estrogen, and testosterone enanthate benzilic acid hydrazone (TEBH), a long-acting androgen/anabolic steroid. EDE has not been made available for medical use alone. The medication, in combination with EB and TEBH, was given by injection into muscle once or at regular intervals, for instance once every 6 weeks.

    Side effects of EDE include breast tenderness, breast enlargement, nausea, headache, and fluid retention. EDE is an estrogen and hence is an agonist of the estrogen receptor, the biological target of estrogens like estradiol. It is an estrogen ester and a prodrug of estradiol in the body. Because of this, it is considered to be a natural and bioidentical form of estrogen.

    EDE was first described by 1959. It was previously available in Canada and Germany but was discontinued by 2005. The medication is no longer available in any form.

    Medical uses

    EDE, a long-acting estrogen, was used in combination with EB, a short-acting estrogen, and TEBH, a long-acting androgen/anabolic steroid, in menopausal hormone therapy in perimenopausal, postmenopausal, hypogonadal, and oophorectomized women, as well as for suppression of lactation in postpartum women.

    Available forms

    See also: Estradiol benzoate/estradiol dienanthate/testosterone enanthate benzilic acid hydrazone

    EDE was available only in combination EB and TEBH. The combination was available in two different dose forms, one for menopausal hormone therapy (brand names Climacteron, Amenose) and the other for lactation suppression (brand names Lactimex, Lactostat). Climacteron and Amenose contained 1.0 mg EB, 7.5 mg EDE, and 150 mg TEBH (69 mg free testosterone) and was given by repeated intramuscular injection at regular intervals. Lactimex and Lactostat contained 6 mg EB, 15 mg EDE, and 300 mg TEBH in 2 mL of corn oil and was administered as a single intramuscular injection after childbirth or during breastfeeding.

    Pharmacology

    Estradiol, the active form of EDE.

    Pharmacodynamics

    See also: Pharmacodynamics of estradiol

    EDE is an estradiol ester, or a prodrug of estradiol. As such, it is an estrogen, or an agonist of the estrogen receptors. EDE is of about 82% higher molecular weight than estradiol due to the presence of its C3 and C17β heptanoate (enanthate) esters. Because EDE is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.

    Potencies and durations of natural estrogens by intramuscular injection
    Estrogen Form Dose (mg) Duration by dose (mg)
    EPD CICD
    Estradiol Aq. soln. ? – <1 d
    Oil soln. 40–60 – 1–2 ≈ 1–2 d
    Aq. susp. ? 3.5 0.5–2 ≈ 2–7 d; 3.5 ≈ >5 d
    Microsph. ? – 1 ≈ 30 d
    Estradiol benzoate Oil soln. 25–35 – 1.66 ≈ 2–3 d; 5 ≈ 3–6 d
    Aq. susp. 20 – 10 ≈ 16–21 d
    Emulsion ? – 10 ≈ 14–21 d
    Estradiol dipropionate Oil soln. 25–30 – 5 ≈ 5–8 d
    Estradiol valerate Oil soln. 20–30 5 5 ≈ 7–8 d; 10 ≈ 10–14 d;
    40 ≈ 14–21 d; 100 ≈ 21–28 d
    Estradiol benz. butyrate Oil soln. ? 10 10 ≈ 21 d
    Estradiol cypionate Oil soln. 20–30 – 5 ≈ 11–14 d
    Aq. susp. ? 5 5 ≈ 14–24 d
    Estradiol enanthate Oil soln. ? 5–10 10 ≈ 20–30 d
    Estradiol dienanthate Oil soln. ? – 7.5 ≈ >40 d
    Estradiol undecylate Oil soln. ? – 10–20 ≈ 40–60 d;
    25–50 ≈ 60–120 d
    Polyestradiol phosphate Aq. soln. 40–60 – 40 ≈ 30 d; 80 ≈ 60 d;
    160 ≈ 120 d
    Estrone Oil soln. ? – 1–2 ≈ 2–3 d
    Aq. susp. ? – 0.1–2 ≈ 2–7 d
    Estriol Oil soln. ? – 1–2 ≈ 1–4 d
    Polyestriol phosphate Aq. soln. ? – 50 ≈ 30 d; 80 ≈ 60 d
    Notes and sources
    Notes: All aqueous suspensions are of microcrystalline particle size. Estradiol production during the menstrual cycle is 30–640 µg/d (6.4–8.6 mg total per month or cycle). The vaginal epithelium maturation dosage of estradiol benzoate or estradiol valerate has been reported as 5 to 7 mg/week. An effective ovulation-inhibiting dose of estradiol undecylate is 20–30 mg/month. Sources: See template.
    Hormone levels with estradiol benzoate/estradiol dienanthate/testosterone enanthate benzilic acid hydrazone by intramuscular injection

    Pharmacokinetics

    See also: Pharmacokinetics of estradiol and Estradiol benzoate/estradiol dienanthate/testosterone enanthate benzilic acid hydrazone

    Estradiol and testosterone levels following a single intramuscular injection of Climacteron (including 1 mg EB, 7.5 mg EDE, and 150 mg TEBH equivalent to 69 mg free testosterone) versus 10 mg estradiol valerate have been studied over 28 days.

    Potencies and durations of natural estrogens by intramuscular injection
    Estrogen Form Dose (mg) Duration by dose (mg)
    EPD CICD
    Estradiol Aq. soln. ? – <1 d
    Oil soln. 40–60 – 1–2 ≈ 1–2 d
    Aq. susp. ? 3.5 0.5–2 ≈ 2–7 d; 3.5 ≈ >5 d
    Microsph. ? – 1 ≈ 30 d
    Estradiol benzoate Oil soln. 25–35 – 1.66 ≈ 2–3 d; 5 ≈ 3–6 d
    Aq. susp. 20 – 10 ≈ 16–21 d
    Emulsion ? – 10 ≈ 14–21 d
    Estradiol dipropionate Oil soln. 25–30 – 5 ≈ 5–8 d
    Estradiol valerate Oil soln. 20–30 5 5 ≈ 7–8 d; 10 ≈ 10–14 d;
    40 ≈ 14–21 d; 100 ≈ 21–28 d
    Estradiol benz. butyrate Oil soln. ? 10 10 ≈ 21 d
    Estradiol cypionate Oil soln. 20–30 – 5 ≈ 11–14 d
    Aq. susp. ? 5 5 ≈ 14–24 d
    Estradiol enanthate Oil soln. ? 5–10 10 ≈ 20–30 d
    Estradiol dienanthate Oil soln. ? – 7.5 ≈ >40 d
    Estradiol undecylate Oil soln. ? – 10–20 ≈ 40–60 d;
    25–50 ≈ 60–120 d
    Polyestradiol phosphate Aq. soln. 40–60 – 40 ≈ 30 d; 80 ≈ 60 d;
    160 ≈ 120 d
    Estrone Oil soln. ? – 1–2 ≈ 2–3 d
    Aq. susp. ? – 0.1–2 ≈ 2–7 d
    Estriol Oil soln. ? – 1–2 ≈ 1–4 d
    Polyestriol phosphate Aq. soln. ? – 50 ≈ 30 d; 80 ≈ 60 d
    Notes and sources
    Notes: All aqueous suspensions are of microcrystalline particle size. Estradiol production during the menstrual cycle is 30–640 µg/d (6.4–8.6 mg total per month or cycle). The vaginal epithelium maturation dosage of estradiol benzoate or estradiol valerate has been reported as 5 to 7 mg/week. An effective ovulation-inhibiting dose of estradiol undecylate is 20–30 mg/month. Sources: See template.

    Chemistry

    See also: Estrogen ester and List of estrogen esters § Estradiol esters

    EDE is a synthetic estrane steroid and the C3 and C17β heptanoate (enanthate) diester of estradiol. It is also known as estradiol 3,17β-heptanoate or as estra-1,3,5(10)-triene-3,17β-diol 3,17β-diheptanoate. EDE is structurally related to estradiol enanthate (estradiol 17β-heptanoate), which has a single heptanoate ester rather than two.

    Structural properties of selected estradiol esters
    Estrogen Structure Ester(s) Relative
    mol. weight     		Relative
    E2 contentb     		log Pc
    Position(s) Moiet(ies) Type Lengtha
    Estradiol
    Estradiol.svg
    		 – – – – 1.00 1.00 4.0
    Estradiol acetate
    Estradiol 3-acetate.svg
    		 C3 Ethanoic acid Straight-chain fatty acid 2 1.15 0.87 4.2
    Estradiol benzoate
    Estradiol benzoate.svg
    		 C3 Benzenecarboxylic acid Aromatic fatty acid – (~4–5) 1.38 0.72 4.7
    Estradiol dipropionate
    Estradiol dipropionate.svg
    		 C3, C17β Propanoic acid (×2) Straight-chain fatty acid 3 (×2) 1.41 0.71 4.9
    Estradiol valerate
    Estradiol valerate.svg
    		 C17β Pentanoic acid Straight-chain fatty acid 5 1.31 0.76 5.6–6.3
    Estradiol benzoate butyrate
    Estradiol butyrate benzoate.svg
    		 C3, C17β Benzoic acid, butyric acid Mixed fatty acid – (~6, 2) 1.64 0.61 6.3
    Estradiol cypionate
    Estradiol 17 beta-cypionate.svg
    		 C17β Cyclopentylpropanoic acid Aromatic fatty acid – (~6) 1.46 0.69 6.9
    Estradiol enanthate
    Estradiol enanthate.png
    		 C17β Heptanoic acid Straight-chain fatty acid 7 1.41 0.71 6.7–7.3
    Estradiol dienanthate
    Estradiol dienanthate.svg
    		 C3, C17β Heptanoic acid (×2) Straight-chain fatty acid 7 (×2) 1.82 0.55 8.1–10.4
    Estradiol undecylate
    Estradiol undecylate.svg
    		 C17β Undecanoic acid Straight-chain fatty acid 11 1.62 0.62 9.2–9.8
    Estradiol stearate
    Estradiol stearate structure.svg
    		 C17β Octadecanoic acid Straight-chain fatty acid 18 1.98 0.51 12.2–12.4
    Estradiol distearate
    Estradiol distearate.svg
    		 C3, C17β Octadecanoic acid (×2) Straight-chain fatty acid 18 (×2) 2.96 0.34 20.2
    Estradiol sulfate
    Estradiol sulfate.svg
    		 C3 Sulfuric acid Water-soluble conjugate – 1.29 0.77 0.3–3.8
    Estradiol glucuronide
    Estradiol sulfate.svg
    		 C17β Glucuronic acid Water-soluble conjugate – 1.65 0.61 2.1–2.7
    Estramustine phosphated
    Estramustine phosphate.svg
    		 C3, C17β Normustine, phosphoric acid Water-soluble conjugate – 1.91 0.52 2.9–5.0
    Polyestradiol phosphatee
    Polyestradiol phosphate.svg
    		 C3–C17β Phosphoric acid Water-soluble conjugate – 1.23f 0.81f 2.9g
    Footnotes: a = Length of ester in carbon atoms for straight-chain fatty acids or approximate length of ester in carbon atoms for aromatic fatty acids. b = Relative estradiol content by weight (i.e., relative estrogenic exposure). c = Experimental or predicted octanol/water partition coefficient (i.e., lipophilicity/hydrophobicity). Retrieved from PubChem, ChemSpider, and DrugBank. d = Also known as estradiol normustine phosphate. e = Polymer of estradiol phosphate (~13 repeat units). f = Relative molecular weight or estradiol content per repeat unit. g = log P of repeat unit (i.e., estradiol phosphate). Sources: See individual articles.

    History

    EDE was first described and introduced for medical use by 1959.

    Society and culture

    Brand names

    EDE was marketed in combination with EB and TEBH under the brand names Climacteron, Amenose, Lactimex, and Lactostat.

    Availability

    EDE is no longer available but was previously used in Canada, Germany and other countries.

    See also


    Новое сообщение