| Candidate ID: | R0132 |
| Source ID: | DB00367 |
| Source Type: | approved; investigational |
| Compound Type: |
small molecule
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| Compound Name: |
Levonorgestrel
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| Synonyms: |
(-)-13-Ethyl-17-hydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one; (8R,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-17-hydroxy- 1,2,6,7,8,9,10,11,12,13,14,15,16, 17- tetradecahydrocyclopenta[a] phenanthren-3-one; 13-beta-Ethyl-17alpha-ethynyl-17beta-hydroxygon-4-en-3-one; 13-Ethyl-17-alpha-ethynyl-17-beta-hydroxy-4-gonen-3-one; 13-Ethyl-17-alpha-ethynylgon-4-en-17-beta-ol-3-one; 17-alpha-Ethinyl-13-beta-ethyl-17-beta-hydroxy-4-estren-3-one; 17-alpha-Ethynyl-13-ethyl-19-nortestosterone; 17-Ethynyl-18-methyl-19-nortestosterone; 17alpha-Ethynyl-13beta-ethyl-3-oxo-4-estren-17beta-ol; 17alpha-Ethynyl-17-hydroxy-18-methylestr-4-en-3-one; 17alpha-Ethynyl-18-homo-19-nortestosterone; 18-Methyl-17-alpha-ethynyl-19-nortestosterone; 18-Methylnorethisterone; d(-)-Norgestrel
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| Molecular Formula: |
C21H28O2
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| SMILES: |
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(CC)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: |
Levonorgestrel (LNG) is a synthetic progestogen similar to used in contraception and hormone therapy. Also known as Plan B, it is used as a single agent in emergency contraception, and as a hormonal contraceptive released from an intrauterine device, commonly referred to as an IUD. Some of these devices are known as Jaydess, Kyleena, and Mirena. A subdermal implant of levonorgestrel that slowly releases the hormone over a long-term period is also available. In addition to the above uses, levonorgestrel is used as a component of long-term combination contraceptives.
Globally, levonorgestrel is the most commonly used emergency contraceptive. It was initially granted FDA approval in 1982 and was the first emergency contraceptive containing only progesterone, showing high levels of efficacy and a lack of estrogenic adverse effects when compared to older emergency contraceptive regimens.
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| CAS Number: |
797-63-7
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| Molecular Weight: |
312.4458
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| DrugBank Indication: |
**Emergency contraception**
Levonorgestrel, in the single-agent emergency contraceptive form, is indicated for the prevention of pregnancy after the confirmed or suspected failure of contraception methods or following unprotected intercourse. It is distributed by prescription for patients under 17, and over the counter for those above this age. This levonorgestrel-only form of contraception is not indicated for regular contraception and must be taken as soon as possible within 72 hours after intercourse. It has shown a lower efficacy when it is used off label within 96 hours.
**Long-term contraception or nonemergency contraception**
In addition to the above indication in emergency contraception, levonorgestrel is combined with other contraceptives in contraceptive formulations designed for regular use, for example with ethinyl estradiol. It is used in various hormone-releasing intrauterine devices for long-term contraception ranging for a duration of 3-5 years. Product labeling for Mirena specifically mentions that it is recommended in women who have had at least 1 child. A subdermal implant is also available for the prevention of pregnancy for up to 5 years.
**Hormone therapy and off-label uses**
Levonorgestrel is prescribed in combination with estradiol as hormone therapy during menopause to manage vasomotor symptoms and to prevent osteoporosis.Off-label, levonorgestrel may be used to treat menorrhagia, endometrial hyperplasia, and endometriosis.
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| DrugBank Pharmacology: |
Levonorgestrel prevents pregnancy by interfering with ovulation, fertilization, and implantation. The levonorgestrel-only containing emergency contraceptive tablet is 89% effective if it is used according to prescribing information within 72 hours after intercourse. The intrauterine and implantable devices releasing levonorgestrel are more than 99% in preventing pregnancy. Levonorgestrel utilized as a component of hormonal therapy helps to prevent endometrial carcinoma associated with unopposed estrogen administration.
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| DrugBank MoA: |
**Mechanism of action on ovulation**
Oral contraceptives containing levonorgestrel suppress gonadotropins, inhibiting ovulation. Specifically, levonorgestrel binds to progesterone and androgen receptors and slows the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This process results in the suppression of the normal physiological luteinizing hormone (LH) surge that precedes ovulation. It inhibits the rupture of follicles and viable egg release from the ovaries. Levonorgestrel has been proven to be more effective when administered before ovulation.
**Mechanism of action in cervical mucus changes**
Similar to other levonorgestrel-containing contraceptives, the intrauterine (IUD) forms of levonorgestrel likely prevent pregnancy by increasing the thickness of cervical mucus, interfering with the movement and survival of sperm, and inducing changes in the endometrium, where a fertilized ovum is usually implanted. Levonorgestrel is reported to alter the consistency of mucus in the cervix, which interferes with sperm migration into the uterus for fertilization. Levonorgestrel is not effective after implantation has occurred.
Interestingly, recent evidence has refuted the commonly believed notion that levonorgestrel changes the consistency of cervical mucus when it is taken over a short-term period, as in emergency contraception. Over a long-term period, however, levonorgestrel has been proven to thicken cervical mucus. The exact mechanism of action of levonorgestrel is not completely understood and remains a topic of controversy and ongoing investigation.
*Effects on implantation**
The effects of levonorgestrel on endometrial receptivity are unclear, and the relevance of this mechanism to the therapeutic efficacy of levonorgestrel is contentious. Prescribing information for levonorgestrel IUDs state that they exert local morphological changes to the endometrium (e.g. stromal pseudodecidualization, glandular atrophy) that may play a role in their contraceptive activity.
**Mechanism of action in hormone therapy**
When combined with estrogens for the treatment of menopausal symptoms and prevention of osteoporosis, levonorgestrel serves to lower the carcinogenic risk of unopposed estrogen therapy via the inhibition of endometrial proliferation. Unregulated endometrial proliferation sometimes leads to endometrial cancer after estrogen use.
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| Targets: |
Progesterone receptor modulator; 3-oxo-5-alpha-steroid 4-dehydrogenase 1 inhibitor; Estrogen receptor alpha other/unknown; Androgen receptor binder; Sex hormone-binding globulin inhibitor&binder; Glucocorticoid receptor binder
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| Inclusion Criteria: |
Indication associated
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