Antiandrogenic properties of nomegestrol acetate.
Nomegestrol acetate (NOM-Ac; TX 066, 17 alpha-acetoxy-6-methyl-19-nor-4,6-pregnadiene-3,20-dione, CAS 58652-20-3), a 19-nor-progesterone derivative showed a significant antiandrogenic effect on ventral prostate and seminal vesicles weights of immature castrated rats treated with testosterone. However, this effect was 20 times less potent than that of cyproterone acetate (CYP-Ac). In contrast to norethindrone acetate, a 19-nor-testosterone derivative. NOM-Ac was totally devoid of androgenic effect on male accessory sex organs. Relative binding affinity against 3H-testosterone for androgen receptor of rat ventral prostate showed an IC50 of 22.6 +/- 4.0 and 21.1 +/- 5.3 nmol/l for NOM-Ac and CYP-Ac, respectively, while Dixon analysis disclosed a Ki of 7.58 +/- 0.94 and 4.30 +/- 0.17 nmol/l. Then, Scatchard plot analysis of 3H-NOM-Ac binding revealed a KD of 20.9 +/- 3.1 nmol/l and a Bmax of 217 +/- 27 fmol/mg protein.
Duc
I
I
Preclinical Research and Development Department, Théramex Laboratories, Monaco.
Botella
J
J
Bonnet
P
P
Fraboul
F
F
Delansorne
R
R
Paris
J
J
D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D017373:Cyproterone Acetate / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005837:Genitalia, Male / Q000187:drug effects; D008297:Male; D008535:Megestrol; D009640:Norethindrone / Q000494:pharmacology; D009649:Norpregnadienes / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D045167:Progesterone Congeners / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects
D000726:Androgen Antagonists; D009649:Norpregnadienes; D045167:Progesterone Congeners; D011506:Proteins; D011944:Receptors, Androgen; D013739:Testosterone; D017373:Cyproterone Acetate; C038501:nomegestrol acetate; D008535:Megestrol; D009640:Norethindrone