Trestolone

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Trestolone
Accession Number
DB05830
Type
Small Molecule
Groups
Investigational
Description

Trestolone (7α-methyl-19-nortestosterone) is a synthetic androgen developed by the Population Council as a potential candidate drug for use in hormonal male contraceptive methods. In males, regular administration of sufficient quantities of trestolone induces a state of temporary infertility.

Structure
Thumb
Synonyms
  • 17beta-Hydroxy-7alpha-methylestr-4-en-3-one
  • 17beta-Hydroxy-7alpha-methylestr-4-enone
  • 19-Nor-7alpha-methyltestosterone
  • 19-Nor-methyltestosterone
  • 7alpha-Methyl-17beta-hydroxy-4-estren-3-one
  • 7alpha-Methyl-19-nortestosterone
  • 7alpha-Methyl-3-oxo-4-estren-17beta-ol
  • 7alpha-Methylnandrolone
  • 7α-methyl-19-nortestosterone
  • MENT
  • Trestolona
  • Trestolonum
External IDs
RU 27333
International/Other Brands
MENT
Categories
UNII
40P3287I94
CAS number
3764-87-2
Weight
Average: 288.431
Monoisotopic: 288.208930142
Chemical Formula
C19H28O2
InChI Key
YSGQGNQWBLYHPE-CFUSNLFHSA-N
InChI
InChI=1S/C19H28O2/c1-11-9-12-10-13(20)3-4-14(12)15-7-8-19(2)16(18(11)15)5-6-17(19)21/h10-11,14-18,21H,3-9H2,1-2H3/t11-,14+,15-,16+,17+,18-,19+/m1/s1
IUPAC Name
(1S,3aS,3bR,4R,9aR,9bS,11aS)-1-hydroxy-4,11a-dimethyl-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-7-one
SMILES
[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3C[C@@H](C)[C@@]21[H]

Pharmacology

Indication

Investigated for use/treatment in contraception and male hormonal deficiencies/abnormalities.

Pharmacodynamics
Not Available
Mechanism of action

Spermatozoa are produced in the testes of males in a process called spermatogenesis. In order to render a man infertile, a hormone-based male contraceptive method must stop spermatogenesis by interrupting the release of gonadotropins from the pituitary gland. Even in low concetrations, trestolone is a potent inhibitor of the release of the gonadotropin hormones, luteinizing hormone (LH) and follicle stimulating hormone (FSH).

In order for spermatogenesis to occur in the testes, both FSH and the male hormone testosterone must be present. By inhibiting release of FSH, trestolone creates an endocrine environment in which conditions for spermatogenesis are not ideal. Manufacture of sperm is further impaired by the suppression of LH, which in turn drastically cutails the production of testosterone. Sufficient regular doses of trestolone cause severe oligozoospermia or azoospermia, and therefore infertility, in most male patients.

Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe therapeutic efficacy of (R)-warfarin can be increased when used in combination with Trestolone.
(S)-WarfarinThe therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Trestolone.
4-hydroxycoumarinThe therapeutic efficacy of 4-hydroxycoumarin can be increased when used in combination with Trestolone.
AbciximabThe therapeutic efficacy of Abciximab can be increased when used in combination with Trestolone.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Trestolone.
AcetaminophenThe metabolism of Trestolone can be increased when combined with Acetaminophen.
Acetylsalicylic acidThe therapeutic efficacy of Acetylsalicylic acid can be increased when used in combination with Trestolone.
AldosteroneThe risk or severity of edema formation can be increased when Trestolone is combined with Aldosterone.
AlimemazineThe metabolism of Trestolone can be increased when combined with Alimemazine.
AlteplaseThe therapeutic efficacy of Alteplase can be increased when used in combination with Trestolone.
Food Interactions
Not Available

References

General References
  1. Walton MJ, Kumar N, Baird DT, Ludlow H, Anderson RA: 7alpha-methyl-19-nortestosterone (MENT) vs testosterone in combination with etonogestrel implants for spermatogenic suppression in healthy men. J Androl. 2007 Sep-Oct;28(5):679-88. Epub 2007 Apr 25. [PubMed:17460095]
  2. Ramachandra SG, Ramesh V, Krishnamurthy HN, Kumar N, Sundaram K, Hardy MP, Rao AJ: Effect of chronic administration of 7alpha-methyl-19-nortestosterone on serum testosterone, number of spermatozoa and fertility in adult male bonnet monkeys (Macaca radiata). Reproduction. 2002 Aug;124(2):301-9. [PubMed:12141943]
External Links
PubChem Compound
19582
PubChem Substance
175427041
ChemSpider
8014619
Wikipedia
Trestolone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceBlood Pressures1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0391 mg/mLALOGPS
logP2.65ALOGPS
logP3.35ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)18.34ChemAxon
pKa (Strongest Basic)-0.88ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity84.5 m3·mol-1ChemAxon
Polarizability33.92 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.973
Caco-2 permeable+0.8984
P-glycoprotein substrateSubstrate0.6498
P-glycoprotein inhibitor IInhibitor0.5489
P-glycoprotein inhibitor IINon-inhibitor0.8923
Renal organic cation transporterNon-inhibitor0.7324
CYP450 2C9 substrateNon-substrate0.8167
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7739
CYP450 1A2 substrateNon-inhibitor0.9005
CYP450 2C9 inhibitorNon-inhibitor0.95
CYP450 2D6 inhibitorNon-inhibitor0.9452
CYP450 2C19 inhibitorNon-inhibitor0.6668
CYP450 3A4 inhibitorNon-inhibitor0.8812
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8683
Ames testNon AMES toxic0.9382
CarcinogenicityNon-carcinogens0.9483
BiodegradationNot ready biodegradable0.9174
Rat acute toxicity1.6259 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8938
hERG inhibition (predictor II)Non-inhibitor0.7163
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Drug created on November 18, 2007 11:28 / Updated on November 02, 2018 06:12