Identification

Name
Medrogestone
Accession Number
DB09124
Type
Small Molecule
Groups
Approved
Description

Medrogestone (INN), also known as 6,17α-dimethyl-6-dehydroprogesterone, is a progestational agent derived from 17-methylprogesterone. It was conceived as an alternative for an orally effective option.[1] It was developed by Ayerst, approved in Canada in 1969 and its current status is cancelled post-marketing.[7] It was never approved by the FDA.

Structure
Thumb
Synonyms
Not Available
External IDs
AY 62022 / AY-13615 / AY-13615S / AY-62022 / NSC-123018
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Colprone Tab 5mgTablet5 mgOralWyeth Ayerst Canada Inc.1996-10-252001-08-30Canada
Colprone Tab 5mgTablet5 mgOralAyerst Laboratories1969-12-311997-08-15Canada
Categories
UNII
077DN93G5B
CAS number
977-79-7
Weight
Average: 340.507
Monoisotopic: 340.24023027
Chemical Formula
C23H32O2
InChI Key
HCFSGRMEEXUOSS-JXEXPEPMSA-N
InChI
InChI=1S/C23H32O2/c1-14-12-17-18(21(3)9-6-16(25)13-20(14)21)7-11-23(5)19(17)8-10-22(23,4)15(2)24/h12-13,17-19H,6-11H2,1-5H3/t17-,18+,19+,21-,22-,23+/m1/s1
IUPAC Name
(1S,2R,10R,11S,14S,15S)-14-acetyl-2,8,14,15-tetramethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-6,8-dien-5-one
SMILES
[H][C@@]12CC[C@](C)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])C=C(C)C2=CC(=O)CC[C@]12C

Pharmacology

Indication

Medrogestone is indicated as adjunct to treat endometial shedding in menopausal women, to treat secondary amenorrhea, to induce menses and to treat dysfunctional uterine bleeding in adult and adolescent women.[2]

Pharmacodynamics

Medrogestone was created as a more potent and orally active option of progesterone. In pre-clinical trials, medrogestone was proven to have four times more progestational activity than progesterone with a similar duration effect than the one found for 17-hydroxyprogesterone. Medrogestone was also able to maintain pregnancy and prevented ovulation in ovariectomized rats. Administration of medrogestone, alone or with premarin, prevented pregnancy, as well as it suppressed ovarian weight increase by nearly 100% of the tested individuals. Medrogestone does not produce any androgenic effect but it presented a marked anti-androgenic effect. It did not present an oestrogenic effect, nor changes in organ weight or histological appearance in adrenal glands or thymus and it does not present any anti-inflammatory effects.[1]

Mechanism of action

Medrogestone is a progestogen, thus its action is done under the same profile. These type of molecules are steroid hormones that bind and activate the progesterone receptor.[3] Its action may involve the suppression of gonadotropic hormones from the anterior portion of the pituitary gland and secondary suppression of testosterone. Medrogestone presents structural similarities to testosterone which allows it to compete for the androgen-receptor-protein receptor sites in prostatic cells.[4] Administration of medrogestone diminishes the response to endogenous hormones in tumor cells due to a reduction in hormone steroid receptors; this effect will translate into cytotoxic or antiproliferative effects.[2]

TargetActionsOrganism
AProgesterone receptor
ligand
Human
Absorption

When administered, medrogestone presents a very rapid gastrointestinal absorption with a bioavailability of 100%. The maximum serum concentration of medrogestone is 10-15 ng/ml.[5]

Volume of distribution
Not Available
Protein binding

Medrogestone, as presented for all progestogens, is highly bound to plasma proteins. It is mainly bound to albumin but it also binds to other plasma proteins like sex hormone binding globulin or corticosteroid-binding globulin.[5] The pharmacokinetics of medrogestone will depend on the degree of plasma protein bindind which makes this characteristic the main regulator of the tissue availability of medrogestone.[6]

Metabolism

The non-protein bound fraction of medrogestoneis available for metabolism.[6] The main route in the metabolism of medrogestone is hydroxylation.[5]

Route of elimination

The elimination time of medrogestone is of 36 hours.[5]

Half life

The half-life of medrogestone is reported to be of 4 hours.[5]

Clearance
Not Available
Toxicity

There were reports of increased urinary flow rates and total micturition volumes as well as sexual dysfunction and hyperglycemia.[4]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINEThe serum concentration of (1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINE can be decreased when it is combined with Medrogestone.
2,4-thiazolidinedioneThe serum concentration of 2,4-thiazolidinedione can be decreased when it is combined with Medrogestone.
AbciximabMedrogestone may decrease the anticoagulant activities of Abciximab.
AcarboseThe serum concentration of Acarbose can be decreased when it is combined with Medrogestone.
AcenocoumarolMedrogestone may decrease the anticoagulant activities of Acenocoumarol.
AcetohexamideThe serum concentration of Acetohexamide can be decreased when it is combined with Medrogestone.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Medrogestone.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Medrogestone.
Acetylsalicylic acidMedrogestone may decrease the anticoagulant activities of Acetylsalicylic acid.
AICA ribonucleotideThe serum concentration of AICA ribonucleotide can be decreased when it is combined with Medrogestone.
Food Interactions
Not Available

References

General References
  1. Revesz C, Chappel CI: Biological activity of medrogestone: a new orally active progestin. J Reprod Fertil. 1966 Dec;12(3):473-87. [PubMed:4288903]
  2. Jones & Bartlett (2016). 2016 Nurse's drug handbook (15th ed., pp. 985). Jones and Bartlett Publishers Inc..
  3. Clark M., Harvey R., Finkel R., Rey J. and Whalen K. (2011). Pharmacology (5th ed.). Lippincott Williams & Wilkins.
  4. Hinman F. (1983). Benign prostatic hypertrophy (1st ed.). Kingsport Press.
  5. Lobo R., Crosignani P., Paoletti R. and Bruschi F. (2002). Women's health and menopause (1st ed.). Kluwer Academic Publishers.
  6. Carp H. (2015). Progestogens in obstetrics and gynecology.. Springer.
  7. Health Canada [Link]
External Links
PubChem Compound
9949848
PubChem Substance
310265040
ChemSpider
8125459
ChEBI
135446
ChEMBL
CHEMBL2106825
Wikipedia
Medrogestone
ATC Codes
G03FB07 — Medrogestone and estrogenG03DB03 — Medrogestone
MSDS
Download (78.8 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral5 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)144-146ºC'MSDS'
boiling point (°C)467.17ºC at 760 mmHg'MSDS'
water solubility5.34e-06 mol/L'MSDS'
logP4.45'MSDS'
Predicted Properties
PropertyValueSource
Water Solubility0.00404 mg/mLALOGPS
logP4.35ALOGPS
logP4.59ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)19.18ChemAxon
pKa (Strongest Basic)-4.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity102.6 m3·mol-1ChemAxon
Polarizability40.37 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Pregnane steroids
Direct Parent
Gluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
20-oxosteroids / 3-oxosteroids / Cyclohexenones / Organic oxides / Hydrocarbon derivatives
Substituents
Progestogin-skeleton / 20-oxosteroid / Oxosteroid / 3-oxosteroid / Cyclohexenone / Cyclic ketone / Ketone / Organic oxygen compound / Organic oxide / Hydrocarbon derivative
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Ligand
General Function
Zinc ion binding
Specific Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
References
  1. Clark M., Harvey R., Finkel R., Rey J. and Whalen K. (2011). Pharmacology (5th ed.). Lippincott Williams & Wilkins.

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Binkowska M, Woron J: Progestogens in menopausal hormone therapy. Prz Menopauzalny. 2015 Jun;14(2):134-43. doi: 10.5114/pm.2015.52154. Epub 2015 Jun 22. [PubMed:26327902]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Lobo R., Crosignani P., Paoletti R. and Bruschi F. (2002). Women's health and menopause (1st ed.). Kluwer Academic Publishers.
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Binder
General Function
Androgen binding
Specific Function
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
Gene Name
SHBG
Uniprot ID
P04278
Uniprot Name
Sex hormone-binding globulin
Molecular Weight
43778.755 Da
References
  1. Carp H. (2015). Progestogens in obstetrics and gynecology.. Springer.
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Binder
General Function
Steroid binding
Specific Function
Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
Gene Name
SERPINA6
Uniprot ID
P08185
Uniprot Name
Corticosteroid-binding globulin
Molecular Weight
45140.49 Da
References
  1. Carp H. (2015). Progestogens in obstetrics and gynecology.. Springer.

Drug created on September 23, 2015 10:20 / Updated on August 02, 2018 06:14