Nomegestrol Acetate

Nomegestrol acetate (NOMAC) is a synthetic progestogen used in hormonal contraceptives, hormone replacement therapy, and for the treatment of gynecological disorders. It is available internationally, but not in the US.

Tags
nomegestrol acetate

Identifiers

Abbreviation

NOMAC

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References

Names

  • 17α-acetoxy-6-methyl-19-nor-pregna-4,6-diene-3,20-dione
  • 6-methyl-3,20-dioxo-19-norpregna-4,6-dien-17-yl acetate

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References

CASRN

58652-20-3

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References

PubChem CID

91668

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ECHA InfoCard

  • 100.055.781
  • EC / List #: 261-379-8

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UNII

83J78V5W05

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KEGG Entry Number

D08281

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Wikipedia Entry Name

Nomegestrol Acetate

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ChEBI ID

CHEBI:135564

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ChEMBL ID

CHEMBL1476022

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ChemSpider ID

82771

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Physical & Chemical Properties

Molecular Formula

C23H30O4

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References

Molecular Weight

370.4819 g/mol

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References

Appearance

White or almost white crystalline powder

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References

  1. British Pharmacopoeia 2017: Nomegestrol Acetate monograph
  2. (View all citations for this reference)

Melting Point

214-215° C

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References

  1. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
  2. (View all citations for this reference)

Solubility

Practically insoluble in water, freely soluble in acetone, soluble in ethanol (96%)

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References

  1. British Pharmacopoeia 2017: Nomegestrol Acetate monograph
  2. (View all citations for this reference)

Specific Optical Rotation

-62.6 in absolute ethanol at 22° C; -60 to -64 in absolute ethanol at 25° C

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References

  1. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
  2. (View all citations for this reference)

Toxicology

GHS Hazard Code(s)

Class Category Code Description
Reproductive Toxicity 2 H361 Suspected of damaging fertility or the unborn child
Reproductive Toxicity 1B H360 May damage fertility or the unborn child

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Side Effects

Abnormal bleeding/spotting, headache, hot flushes

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References

  1. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
  2. (View all citations for this reference)

LD50

LD50, mouse intraperitoneal: > 2 g/kg
LD50, mouse oral: > 2 g/kg
LD50, rat intraperitoneal: > 2 g/kg
LD50, rat oral: >2 g/kg
(TDLo), women oral: 1.05 mg/kg

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Safety Profile Overview

Generally very well tolerated, positive safety profile

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References

  1. Africander, D.; Verhoog, N.; Hapgood, J. P., Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception. Steroids 2011, 76 (7), 636-52.
  2. (View all citations for this reference)
  3. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
  4. (View all citations for this reference)

Biochemistry & Pharmacology

Progesterone Receptor Activity

Agonist

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References

Androgen Receptor Activity

Binds but no agonist activity. "Weak," "partial" or "moderate" antagonist.

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References

  1. Africander, D.; Verhoog, N.; Hapgood, J. P., Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception. Steroids 2011, 76 (7), 636-52.
  2. (View all citations for this reference)
  3. Kuhl, H., Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005, 8 Suppl 1, 3-63.
  4. (View all citations for this reference)
  5. Su, Y.; Lian, Q. Q.; Ge, R. S., Contraceptives with novel benefits. Expert Opin Investig Drugs 2012, 21 (1), 83-90.
  6. (View all citations for this reference)
  7. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
  8. (View all citations for this reference)
  9. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
  10. (View all citations for this reference)
  11. Hapgood, J. P.; Africander, D.; Louw, R.; Ray, R. M.; Rohwer, J. M., Potency of progestogens used in hormonal therapy: toward understanding differential actions. J Steroid Biochem Mol Biol 2013, 142, 39-47.
  12. (View all citations for this reference)
  13. Mueck, A. O.; Sitruk-Ware, R., Nomegestrol acetate, a novel progestogen for oral contraception. Steroids 2011, 76 (6), 531-539.
  14. (View all citations for this reference)
  15. Shields-Botella, J.; Duc, I.; Duranti, E.; Puccio, F.; Bonnet, P.; Delansorne, R.; Paris, J., An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells. J. Steroid Biochem. Mol. Biol. 2003, 87 (2-3), 111-122. (View all citations for this reference)

Estrogen Receptor Activity

Antagonist

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References

  1. Su, Y.; Lian, Q. Q.; Ge, R. S., Contraceptives with novel benefits. Expert Opin Investig Drugs 2012, 21 (1), 83-90.
  2. (View all citations for this reference)
  3. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
  4. (View all citations for this reference)
  5. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
  6. (View all citations for this reference)
  7. Mueck, A. O.; Sitruk-Ware, R., Nomegestrol acetate, a novel progestogen for oral contraception. Steroids 2011, 76 (6), 531-539.
  8. (View all citations for this reference)
  9. Shields-Botella, J.; Duc, I.; Duranti, E.; Puccio, F.; Bonnet, P.; Delansorne, R.; Paris, J., An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells. J. Steroid Biochem. Mol. Biol. 2003, 87 (2-3), 111-122. (View all citations for this reference)

Glucocorticoid Receptor Activity

No activity

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References

  1. Kuhl, H., Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005, 8 Suppl 1, 3-63.
  2. (View all citations for this reference)
  3. Hapgood, J. P.; Africander, D.; Louw, R.; Ray, R. M.; Rohwer, J. M., Potency of progestogens used in hormonal therapy: toward understanding differential actions. J Steroid Biochem Mol Biol 2013, 142, 39-47.
  4. (View all citations for this reference)
  5. Su, Y.; Lian, Q. Q.; Ge, R. S., Contraceptives with novel benefits. Expert Opin Investig Drugs 2012, 21 (1), 83-90.
  6. (View all citations for this reference)
  7. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
  8. (View all citations for this reference)
  9. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
  10. (View all citations for this reference)

Mineralocorticoid Receptor Activity

No activity

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References

  1. Kuhl, H., Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005, 8 Suppl 1, 3-63.
  2. (View all citations for this reference)
  3. Hapgood, J. P.; Africander, D.; Louw, R.; Ray, R. M.; Rohwer, J. M., Potency of progestogens used in hormonal therapy: toward understanding differential actions. J Steroid Biochem Mol Biol 2013, 142, 39-47.
  4. (View all citations for this reference)
  5. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
  6. (View all citations for this reference)
  7. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
  8. (View all citations for this reference)

Bioavailability

63-65%

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References

  1. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
  2. (View all citations for this reference)
  3. Burke, A., Nomegestrol acetate-17b-estradiol for oral contraception. Patient Prefer Adherence 2013, 7, 607-19.
  4. (View all citations for this reference)
  5. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
  6. (View all citations for this reference)

Elimination Half-Life (t1/2)

45-50 h

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References

  1. Burke, A., Nomegestrol acetate-17b-estradiol for oral contraception. Patient Prefer Adherence 2013, 7, 607-19.
  2. (View all citations for this reference)
  3. Su, Y.; Lian, Q. Q.; Ge, R. S., Contraceptives with novel benefits. Expert Opin Investig Drugs 2012, 21 (1), 83-90.
  4. (View all citations for this reference)
  5. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
  6. (View all citations for this reference)

Serum Protein Binding

98% bound to serum albumin

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References

  1. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
  2. (View all citations for this reference)

Metabolism

CYP3A3, CYP3A4, CYP2A6

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Cmax

12.3 +/- 3.5 ng/mL

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References

  1. Burke, A., Nomegestrol acetate-17b-estradiol for oral contraception. Patient Prefer Adherence 2013, 7, 607-19.
  2. (View all citations for this reference)
  3. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
  4. (View all citations for this reference)

Tmax

1.5-2 h, 2-3 h regardless of dose

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References

  1. Lello, S., Nomegestrol Acetate Pharmacology, Safety Profile and Therapeutic Efficacy. Drugs 2010, 70 (5), 541-559.
  2. (View all citations for this reference)
  3. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
  4. (View all citations for this reference)

Metabolites

Name
Structure
Notes

6 main metabolites, all of which are basically inactive. Metabolized in the liver through hydroxylation by CYP3A3, CYP3A4, CYP2A6.