Pharmacologic properties of CDB(VA)-2914.
CDB(VA)-2914 (17alpha-acetoxy-11beta-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione) is a synthetic steroid that demonstrates potent progesterone antagonist activity in vitro and in vivo. Its binding and antagonist potency with respect to the glucocorticoid receptor is significantly reduced compared to that of mifepristone, indicating that CDB(VA)-2914 belongs to a new class of dissociated progesterone receptor modulators that have reduced antiglucorticoid activity. The pharmacological effects of CDB(VA)-2914 have been examined in a variety of animal models, the results of which are reviewed in this paper. CDB(VA)-2914 inhibits ovulation in rats in a dose-dependent manner upon single-dose oral administration and exhibits antifertility activity during continuous low-dose administration. CDB(VA)-2914 is also effective in animal models of postcoital contraception. This paper also presents the results of metabolism studies undertaken to link the results of the animal models to potential human applications. Because of its unique pharmacological profile, CDB(VA)-2914 is a promising candidate for use in contraception as well as treatment of uterine fibroids and endometriosis.
Gainer
Erin E
EE
HRA Pharma, 19, rue Frédérick Lemaître, Paris 75020, France. gainer@hra-pharma.com
Ulmann
André
A
D000284:Administration, Oral; D000818:Animals; D003283:Contraceptives, Postcoital, Synthetic / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D008956:Models, Chemical; D009649:Norpregnadienes / Q000494:pharmacology*; D011485:Protein Binding; D011980:Receptors, Progesterone / Q000378:metabolism; D013256:Steroids / Q000378:metabolism
D003283:Contraceptives, Postcoital, Synthetic; D005938:Glucocorticoids; D006727:Hormone Antagonists; D009649:Norpregnadienes; D011980:Receptors, Progesterone; D013256:Steroids; D015735:Mifepristone; C094854:ulipristal