Levonorgestrel

Names

[ Name ]:
Levonorgestrel

[Synonym ]:
(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-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one
Mirena
13-Ethyl-17-ethynyl-17b-hydroxy-4-gonen-3-one
17a-Ethynyl-18-homo-19-nortestosterone
Norgeston
13b-Ethyl-17a-ethynyl-17b-hydroxygon-4-en-3-one
18-METHYLNORETHINDRONE
18-Methyl-17a-ethynyl-19-nortestosterone
(−)-Norgestrel
Norplant
(17a)-13-Ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one
Levonelle
13-β-ETHYL-17-α-ETHYNYL-17-β-HYDROXYGON-4-EN-3-ONE
monovar
MFCD01546387
sh850
wy3707
17b-Hydroxy-18-methyl-19-nor-17a-pregn-4-en-20-yn-3-one
(8R,9S,10R,13S,14S,17R)-17-Ethinyl-13-ethyl-17-hydroxy-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-on
Levonova
(8R,9S,10R,13S,14S,17R)-13-éthyl-17-éthynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tétradécahydro-3H-cyclopenta[a]phénanthrén-3-one
17a-Ethynyl-18-methyl-19-nortestosterone
EINECS 212-349-8
17a-Ethynyl-17-hydroxy-18-methylestr-4-en-3-one
D-Norgestrel
Microval
13-Ethyl-17-hydroxy-18,19-dinor-17a-pregn-4-en-20-yn-3-one
Norgestrel
17a-Ethynyl-13-ethyl-19-nortestosterone
Microlut
Ovrette
UNII:3J8Q1747Z2
D(−)-Norgestrel
NorLevo
(17a)-(-)-13-Ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one
D-(-)-Norgestrel
Neogest
(-)-Norgestrel
13-Ethyl-17a-ethynyl-17-hydroxygon-4-en-3-one
fh122-a

Biological Activity

[Description]:

Norgestrel is a synthetic analog of progesterone, a compound commonly found in oral contraceptive pill, and a powerful neuroprotective antioxidant, preventing light-induced ROS in photoreceptor cells, and cell death[1][2].

[Related Catalog]:

Research Areas >> Cancer

[In Vitro]

Norgestrel (20 µM; 24 hours; 661W cells) treatment significantly increases cellular viability after serum deprivation and so it is demonstrated that Norgestrel is neuroprotective to stressed 661W cells[1]. Norgestrel (20 µM; 24 hours; 661W cells) treatment decreases apoptotic induced cleavage of PARP and caspase-3[1]. Norgestrel (20 µM; 6 hours; 661W cells) treatment bFGF is results in a significant upregulation of bFGF mRNA in photoreceptor cells[1]. Cell Viability Assay[1] Cell Line: 661W cells Concentration: 20 µM Incubation Time: 24 hours Result: Significantly increased cellular viability after serum deprivation. Western Blot Analysis[1] Cell Line: 661W cells Concentration: 20 µM Incubation Time: 24 hours Result: Decreased apoptotic induced cleavage of PARP and caspase-3. RT-PCR[1] Cell Line: 661W cells Concentration: 20 µM Incubation Time: 6 hours Result: A significant upregulation of bFGF mRNA over 1 hour.

[In Vivo]

Norgestrel (100 mg/kg; intraperitoneal injection; for 6, 24 or 48 hours; Balb/c mice) treatment can prevent light-induced ROS in photoreceptor cells, and subsequent cell death. Norgestrel acts via post-translational modulation of the major antioxidant transcription factor Nrf2; bringing about its phosphorylation, subsequent nuclear translocation, and increases levels of its effector protein superoxide dismutase 2 (SOD2)[2]. Animal Model: Balb/c mice are born into and maintained in dim cyclic light[2] Dosage: 100 mg/kg; Administration: Intraperitoneal injection; for 6, 24 or 48 hours Result: Increased expression and activation of Nrf2 via phosphorylation on serine 40, increased expression of its target antioxidant superoxide dismutase 2 (SOD2), and reduced mitochondrial oxidative stress.

[References]

[1]. Wyse Jackson AC, et al. The synthetic progesterone Norgestrel is neuroprotective in stressed photoreceptor-like cellsand retinal explants, mediating its effects via basic fibroblast growth factor, protein kinase A and glycogen synthase kinase 3β signalling. Eur J Neurosci. 2016 Apr;43(7):899-911.

[2]. Byrne AM, et al. The synthetic progestin norgestrel modulates Nrf2 signaling and acts as an antioxidant in a model of retinal degeneration. Redox Biol. 2016 Dec;10:128-139.

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
459.1±45.0 °C at 760 mmHg

[ Melting Point ]:
239-241ºC

[ Molecular Formula ]:
C₂₁H₂₈O₂

[ Molecular Weight ]:
312.446

[ Flash Point ]:
195.4±21.3 °C

[ Exact Mass ]:
312.208923

[ PSA ]:
37.30000

[ LogP ]:
3.92

[ Vapour Pressure ]:
0.0±2.6 mmHg at 25°C

[ Index of Refraction ]:
1.571

[ Storage condition ]:
2-8°C

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: JF8225200

CHEMICAL NAME :: 18,19-Dinor-17-alpha-pregn-4-en-20-yn-3-one, 13-ethyl-17-hydroxy-, (+-)-

CAS REGISTRY NUMBER :: 6533-00-2

LAST UPDATED :: 199109

DATA ITEMS CITED :: 27

MOLECULAR FORMULA :: C21-H28-O2

MOLECULAR WEIGHT :: 312.49

WISWESSER LINE NOTATION :: L E5 B666 OV MUTJ E2 FQ F1UU1 -DL

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 5010 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 18,185,1971

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 11200 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Liver - other changes

REFERENCE :: YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 29,1479,1978

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >10 gm/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Liver - other changes

REFERENCE :: YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 29,1479,1978

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 5010 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 18,185,1971

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 7300 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Liver - other changes

REFERENCE :: YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 29,1479,1978

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >9 gm/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Liver - other changes

REFERENCE :: YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 29,1479,1978 ** TUMORIGENIC DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 57 mg/kg/68W-C

TOXIC EFFECTS :: Tumorigenic - neoplastic by RTECS criteria Skin and Appendages - tumors

REFERENCE :: CRSBAW Comptes Rendus des Seances de la Societe de Biologie et de Ses Filiales. (SPPIF, B.P.22, F-41353 Vineuil, France) V.1- 1849- Volume(issue)/page/year: 168,1190,1974 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 18 ug/kg

SEX/DURATION :: female 12 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes

REFERENCE :: FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 23,739,1972

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 4 mg/kg

SEX/DURATION :: female 40 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :: INJFA3 International Journal of Fertility. (Allen Press, 1041 New Hampshire, St., Lawrence, KS 66044) V.1- 1955- Volume(issue)/page/year: 11,401,1966

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 365 ug/kg

SEX/DURATION :: female 52 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :: BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 2,730,1969

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 75 ug/kg

SEX/DURATION :: female 5 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - menstrual cycle changes or disorders Reproductive - Fertility - other measures of fertility

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 12,589,1975

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 30 ug/kg

SEX/DURATION :: female 30 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :: BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 4,489,1968

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 150 mg/kg

SEX/DURATION :: female 15-24 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 123,867,1966

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 525 mg/kg

SEX/DURATION :: female 35 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :: INJFA3 International Journal of Fertility. (Allen Press, 1041 New Hampshire, St., Lawrence, KS 66044) V.1- 1955- Volume(issue)/page/year: 11,389,1966

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 548 ug/kg

SEX/DURATION :: female 49 week(s) pre-mating female 1-22 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 2,59,1970

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 210 mg/kg

SEX/DURATION :: female 14 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - uterus, cervix, vagina

REFERENCE :: FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 24,284,1973

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 5 mg/kg

SEX/DURATION :: female 15-24 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 123,867,1966

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 60 mg/kg

SEX/DURATION :: female 17-20 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - urogenital system

REFERENCE :: AVBIB9 Advances in the Biosciences. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1967- Volume(issue)/page/year: 13,71,1974

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 700 ug/kg

SEX/DURATION :: female 14 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Fertility - other measures of fertility

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 5,57,1972

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 140 mg/kg

SEX/DURATION :: female 14 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - uterus, cervix, vagina

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 5,57,1972

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 12 mg/kg

SEX/DURATION :: male 30 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

REFERENCE :: IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963- Volume(issue)/page/year: 10,159,1972

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 19200 ug/kg

SEX/DURATION :: male 48 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)

REFERENCE :: IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963- Volume(issue)/page/year: 10,159,1972

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Implant

DOSE :: 6 mg/kg

SEX/DURATION :: female 17 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 12,549,1975

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 33 mg/kg

SEX/DURATION :: male 94 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - other effects on male

REFERENCE :: IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963- Volume(issue)/page/year: 7,49,1969

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 180 ug/kg

SEX/DURATION :: female 30 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - uterus, cervix, vagina Reproductive - Maternal Effects - other effects

REFERENCE :: IJMRAQ Indian Journal of Medical Research. (Indian Council of Medical Research, Ansari Nagar, New Delhi 110 029, India) V.1- 1913- Volume(issue)/page/year: 63,1413,1975

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Implant

DOSE :: 600 ug/kg

SEX/DURATION :: female 17 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 12,549,1975 *** REVIEWS *** TOXICOLOGY REVIEW JIMRBV Journal of International Medical Research. (Cambridge Medical Pub. Ltd., 435/437 Wellingborough Rd., Northampton, NN1 4EZ, UK) V.1- 1972- Volume(issue)/page/year: 1,141,1973

Safety Information

[ Hazard Codes ]:
Xn:Harmful

[ Risk Phrases ]:
R20/21/22;R40

[ Safety Phrases ]:
S22-S36

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
JF8259000

Articles

Progestagen-only oral contraceptives: a preliminary report of the action and clinical use of norgestrel and norethisterone.

Drugs 6(3) , 169-81, (1973)

Types of combined oral contraceptives used by US women.

Contraception 86(6) , 659-65, (2012)

We sought to estimate the prevalence of types of combined oral contraceptives (COCs) used among US women.We analyzed interview-collected data from 12,279 women aged 15-44 years participating in the Na...

Newer non-oral hormonal contraception.

BMJ 346 , f341, (2013)