| Candidate ID: | R0253 |
| Source ID: | DB00717 |
| Source Type: | approved |
| Compound Type: |
small molecule
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| Compound Name: |
Norethisterone
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| Synonyms: |
(17alpha)-17-ethynyl-17-hydroxyestra-4,8(14),9-trien-3-one; 17-hydroxy-19-nor-17-α-pregn-4-en-20-yn-3-one; 17-hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one; 17-α-ethynyl-17-hydroxy-4-estren-3-one; 17-α-ethynyl-19-norandrost-4-en-17-β-ol-3-one; 17-α-ethynyl-19-nortestosterone; 17-α-ethynyl-4-estren-17-ol-3-one; 17-β-hydroxy-19-norpregn-4-en-20-yn-3-one; 17α-ethinyl-19-nortestosterone; 17α-ethinylestra-4-en-17β-ol-3-one; 17α-ethynyl-17-hydroxy-4-estren-3-one; 17α-ethynyl-17β-hydroxy-19-norandrost-4-en-3-one; 17α-ethynyl-19-nor-4-androsten-17β-ol-3-one; 17α-ethynyl-19-norandrost-4-en-17β-ol-3-one; 17α-ethynyl-19-nortestosterone; 17α-ethynyl-4-estren-17-ol-3-one; 17β-hydroxy-19-norpregn-4-en-20-yn-3-one; 19-nor-17-α-ethynyl-17-β-hydroxy-4-androsten-3-one; 19-nor-17-α-ethynylandrosten-17-β-ol-3-one; 19-nor-17-α-ethynyltestosterone; 19-Nor-17alpha-ethynyl-17beta-hydroxy-4-androsten-3-one; 19-nor-17α-ethynyl-17β-hydroxy-4-androsten-3-one; 19-nor-17α-ethynylandrosten-17β-ol-3-one; 19-nor-17α-ethynyltestosterone; 19-nor-ethindrone; 19-norethisterone; 4-estren-17α-ethynyl-17β-ol-3-one; Norethindrone; Norethisterone
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| Molecular Formula: |
C20H26O2
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| SMILES: |
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H]
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| Structure: |
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| DrugBank Description: |
Norethisterone, also known as norethindrone, is a synthetic progestational hormone belonging to the 19-nortestosterone-derived class of progestins. It is further classified as a second-generation progestin, along with and its derivatives, and is the active form of several other progestins including and . Norethisterone mimics the actions of endogenous , albeit with a greater potency, and is used on its own or in combination with estrogen derivatives in a variety of applications including contraception and hormone replacement therapy. First derived in 1951 in Mexico City, norethisterone was originally intended for use as a remedy for irregular menstruation and endometriosis, and was not marketed for use as an oral contraceptive until 1962.
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| CAS Number: |
68-22-4
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| Molecular Weight: |
298.4192
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| DrugBank Indication: |
Norethisterone is indicated as an oral contraceptive when given as monotherapy or in combination with an estrogen component, such as or . In combination with an estrogen component, oral norethisterone is also indicated as a hormone replacement therapy in the treatment of postmenopausal osteoporosis and moderate-to-severe vasomotor symptoms arising from menopause. When applied via transdermal patch, the combination of norethisterone and estradiol is indicated for the treatment of hypoestrogenism, vulvovaginal atrophy, and moderate-severe vasomotor symptoms.
Norethisterone, taken in combination with intramuscular , is also indicated for the symptomatic treatment of endometriosis-related pain.
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| DrugBank Pharmacology: |
Norethisterone is a synthetic oral progestin used for contraception or to treat other hormone-related conditions such as menopausal symptoms and endometriosis. As a synthetic progestin, norethisterone acts similarly to endogenous progesterone but with a much higher potency - it acts at the pelvic level to alter cervical and endometrial function, as well as via the inhibition of pituitary hormones that play a role in follicular maturation and ovulation. A small increase in the risk of developing breast cancer has been observed in patients using combined oral contraceptives, with some evidence also implicating progestin-only pills - patients starting hormonal contraception should be advised of this risk and should employ routine breast self-examinations to check for evidence of any developing masses.
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| DrugBank MoA: |
On a molecular level, progestins like norethisterone exert their effects on target cells via binding to progesterone receptors that result in downstream changes to target genes. Target cells are found in the reproductive tract, breast, pituitary, hypothalamus, skeletal tissue, and central nervous system. Contraceptive efficacy is derived mainly from changes to the cervical mucus, wherein norethisterone increases the cell content and viscosity of the mucous to impede sperm transport and migration. Norethisterone also induces a variety of changes to the endometrium - including atrophy, irregular secretion, and suppressed proliferation - that make it inhospitable for implantation. Working via a negative feedback loop, norethisterone also acts on both the hypothalamus and anterior pituitary to suppress the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. Suppression of these hormones prevents follicular development, ovulation, and corpus luteum development.
When used as a component of hormone replacement therapy in menopausal women, norethisterone’s value is mainly in suppressing the growth of the endometrium. As estrogen stimulates endometrial growth, the unopposed use of estrogen in postmenopausal women with an intact uterus can lead to endometrial hyperplasia which can increase the risk of endometrial cancer. The addition of a progestin to a hormone replacement therapy in this population protects against this endometrial hyperplasia and, therefore, lowers the risk associated with the use of hormone replacement therapies.
Norethisterone, along with other progestins and endogenous progesterone, has a low affinity for other steroid receptors, such as the androgen receptor and glucocorticoid receptor. While affinity and agonistic activity at these receptors is minimal, it is thought that androgen receptor agonism is responsible for some of the adverse effects observed with progestin use (e.g. acne, serum lipid changes).
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| Targets: |
Progesterone receptor agonist; Androgen receptor agonist; Glucocorticoid receptor agonist
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| Inclusion Criteria: |
Indication associated
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