Chlormadinone Acetate

Chlormadinone acetate (CMA) is a progestin and antiandrogen. It is used in combined oral contraceptives and in treating gynecological disorders.

Tags
chlormadinone acetate
MOL SDF CML

Identifiers

Abbreviation

CMA

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References

Names

  • 17α-acetoxy-6-chloro-6-dehydroprogesterone
  • 17α-acetoxy-6-chloropregna-4,6-diene-3,20-dione

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References

CASRN

302-22-7

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References

PubChem CID

9324

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References

  1. PubChem: Chlormadinone Acetate (View all citations for this reference)

ECHA InfoCard

  • 100.005.563
  • EC / List #: 206-118-0

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References

  1. ECHA: Chlormadinone Acetate (View all citations for this reference)

UNII

0SY050L61N

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References

  1. UNII: Chlormadinone Acetate (View all citations for this reference)

KEGG Entry Number

D01299

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References

  1. KEGG: Chlormadinone Acetate (View all citations for this reference)

Wikipedia Entry Name

Chlormadinone Acetate

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References

  1. Wikipedia: Chlormadinone Acetate (View all citations for this reference)

ChEBI ID

CHEBI:31394

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References

  1. ChEBI: Chlormadinone Acetate (View all citations for this reference)

ChEMBL ID

CHEMBL110691

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References

  1. ChEMBL: Chlormadinone Acetate (View all citations for this reference)

ChemSpider ID

8963

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References

  1. ChemSpider: Chlormadinone Acetate (View all citations for this reference)

NIST

Chlormadinone Acetate

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References

  1. NIST Chemistry WebBook: Chlormadinone Acetate. (View all citations for this reference)

ATC Code(s)

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References

  1. ECHA: Chlormadinone Acetate (View all citations for this reference)

Physical & Chemical Properties

Molecular Formula

C23H29ClO4

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References

Molecular Weight

404.931 g/mol

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References

Appearance

White to light-yellow, odorless crystals

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References

  1. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)

Melting Point

212-214 ° C

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References

  1. Honma, S.; Iwamura, S.; Iizuka, K.; Kambegawa, A.; Shida, K. Identification and Anti-Androgenic Activity of the Metabolites of 17α-Acetoxy-6-Chloropregna-4,6-Diene-3,20-Dione (Chlormadinone Acetate) in the Rat, Rabbit, Dog and Man. Chem. Pharm. Bull. (Tokyo). 1977, 25 (8), 2019–2031. (View all citations for this reference)
  2. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)

Solubility

Practically insoluble in water, very soluble in chloroform, soluble in acetonitrile, slightly soluble in ethanol and diethyl ether.

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References

  1. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)

Specific Optical Rotation

[α]20D, -10.0° to -14.0° in acetonitrile.
[α]D, +6° in chloroform.

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References

  1. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)

Toxicology

GHS Hazard Code(s)

Class Category Code Description
Carcinogenicity 2 H351 Suspected of causing cancer if inhaled
Reproductive Toxicity 1B H360 May damage fertility or the unborn child
Reproductive Toxicity 1A H360FD May damage fertility. May damage the unborn child
Specific Target Organ Toxicity, Repeated Exposure 2 H373 Causes damage to organs through prolonged or repeated exposure

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References

  1. ECHA: Chlormadinone Acetate (View all citations for this reference)

Carcinogenicity

"Tests have failed to show an increased risk for the development of malign tumours in the livers of oral contraceptive users."

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References

  1. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)

Genotoxicity

Genotoxic to human lymphocytes at certain concentrations as measured by chromosomal aberrations and sister chromatid exchanges.

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References

  1. Siddique, Y. H.; Afzal, M. Evaluation of Genotoxic Potential of Synthetic Progestin Chlormadinone Acetate. Toxicol. Lett. 2004, 153 (2), 221–225. (View all citations for this reference)

LD50

  • rat, mouse oral: 6400 mg/kg
  • mouse intraperitoneal: 3 g/kg

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References

  1. Toxnet: Chlormadinone Acetate. (View all citations for this reference)

MRTD

0.0333 mg/kg/day

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References

  1. DSSTox (FDAMDD) FDA Maximum (Recommended) Daily Dose Database. National Center for Biotechnology Information. PubChem BioAssay Database; AID=1195. (View all citations for this reference)

Biochemistry & Pharmacology

Progesterone Receptor Activity

Agonist

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References

  1. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
  2. KEGG: Chlormadinone Acetate (View all citations for this reference)

Androgen Receptor Activity

Antagonist

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References

  1. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
  2. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
    3. (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)
  4. Kuhl, H., Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005, 8 Suppl 1, 3-63.
    5. (View all citations for this reference)
  5. Krattenmacher, R. Drospirenone: Pharmacology and Pharmacokinetics of a Unique Progestogen. Contraception 2000, 62 (1), 29–38. (View all citations for this reference)
  6. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)

Estrogen Receptor Activity

Antagonist

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References

  1. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
  2. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
    3. (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)
  4. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)

Glucocorticoid Receptor Activity

Agonist

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References

  1. 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.
    2. (View all citations for this reference)
  2. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
    3. (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)
  4. WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
  5. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)

Mineralocorticoid Receptor Activity

No activity

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References

  1. 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.
    2. (View all citations for this reference)
  2. Ruan, X.; Seeger, H.; Mueck, A. O., The pharmacology of nomegestrol acetate. Maturitas 2012, 71 (4), 345-53.
    3. (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)
  4. Krattenmacher, R. Drospirenone: Pharmacology and Pharmacokinetics of a Unique Progestogen. Contraception 2000, 62 (1), 29–38. (View all citations for this reference)
  5. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)

Target Pathways

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References

  1. KEGG: Chlormadinone Acetate (View all citations for this reference)

Elimination Half-Life (t1/2)

Around 34 h (Bouchard), 25 h (Terlinden) for single dose administration, 38 h for multiple dose administration.

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References

  1. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)
  2. Terlinden, R.; Uragg, H.; Göhler, K.; Kneip, C. Pharmacokinetics of Chlormadinone Acetate Following Single and Multiple Oral Dosing of Chlormadinone Acetate (2 Mg) and Ethinylestradiol (0.03 Mg) and Elimination and Clearance of a Single Dose of Radiolabeled Chlormadinone Acetate. Contraception 2006, 74 (3), 239–244. (View all citations for this reference)

Serum Protein Binding

96% bound to albumin, does not bind to SHBG or CBG.

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References

  1. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)

Metabolism

Hepatic.

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References

  1. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)

Excretion

45% in urine, 42% in feces.

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References

  1. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)
  2. Terlinden, R.; Uragg, H.; Göhler, K.; Kneip, C. Pharmacokinetics of Chlormadinone Acetate Following Single and Multiple Oral Dosing of Chlormadinone Acetate (2 Mg) and Ethinylestradiol (0.03 Mg) and Elimination and Clearance of a Single Dose of Radiolabeled Chlormadinone Acetate. Contraception 2006, 74 (3), 239–244. (View all citations for this reference)

Cmax

1.60 +/- 0.46 ng/ml (single dose)
2.21 +/- 0.60, 2.06 +/- 0.47 ng/ml (multiple dose)

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References

  1. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)
  2. Terlinden, R.; Uragg, H.; Göhler, K.; Kneip, C. Pharmacokinetics of Chlormadinone Acetate Following Single and Multiple Oral Dosing of Chlormadinone Acetate (2 Mg) and Ethinylestradiol (0.03 Mg) and Elimination and Clearance of a Single Dose of Radiolabeled Chlormadinone Acetate. Contraception 2006, 74 (3), 239–244. (View all citations for this reference)

Tmax

1.6 +/- 0.4 h (single dose)
1.6 +/- 0.5, 1.4 +/- 0.4 h (multiple dose)

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References

  1. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)

AUC

14.40 +/- 4.39 ng*h/mL (single dose)
19.36 +/- 5.50, 15.90 +/- 3.34 ng*h/mL (multiple dose)

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References

  1. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)

Clearance

152 L/day

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References

  1. Murugesan, K.; Laumas, K. R. Norethynodrel Binding to Human Plasma Proteins. J. Steroid Biochem. 1975, 6 (11–12), 1495–1499. (View all citations for this reference)

Enzyme Interactions

Does not block CYP system.

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References

  1. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)

Transformation of Endometrium

1.5 to 2.0 mg/day

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References

  1. Bouchard, P. Chlormadinone Acetate (CMA) in Oral Contraception - a New Opportunity. Eur. J. Contracept. Reprod. Heal. CARE 2005, 10 (1), 7–11. (View all citations for this reference)

Metabolites

Name
Structure
Notes
2α,3β,15β-Trihydroxychlormadinone Acetate
structure

2α,3α,15β-Trihydroxychlormadinone Acetate
structure

2α,3α-Dihydroxychlormadinone Acetate
structure

One of the principle metabolites in circulation.

2α,3β-Dihydroxychlormadinone Acetate
structure

17α-Acetoxy-5β-pregnan-3β-ol-20-one
structure

View All (9)