title: CDB-2914: anti-progestational/anti-glucocorticoid profile and post-coital anti-fertility activity in rats and rabbits.
abstract: Our goal was to determine the endocrine and post-coital anti-fertility activity of CDB-2914. Concurrent administration of progesterone to rats on day 4 post-mating blocked the anti-fertility activity of a single oral 2 mg dose of CDB-2914. CDB-2914 did not exhibit progestational activity in the oestradiol-primed immature female rabbit at doses that exhibited anti-progestational activity. CDB-2914 antagonized exogenous and endogenous progesterone-stimulated uterine haptoglobin synthesis and secretion in immature and adult mated rabbits respectively. Neither CDB-2914 nor mifepristone exhibited glucocorticoid activity as determined by thymus involution in rats; mifepristone was twice as potent as CDB-2914 in antagonizing glucocorticoid action. Post-coital CDB-2914 treatment resulted in a dose-dependent reduction in implantation sites and pregnancy rates in rabbits. CDB-2914-induced inhibition of uterine weight increase, endometrial glandular arborization and uterine haptoglobin synthesis/secretion correlated with inhibition of pregnancy in mated rabbits. A single oral dose of 64 mg CDB-2914/rabbit was effective at blocking pregnancy when administered on day 4, 5, or 6 post-mating, whereas 32 mg/rabbit was only partially effective in this regard. These data demonstrate that CDB-2914 is a potent, orally active anti-progestin with weak anti-glucocorticoid activity. CDB-2914 inhibited implantation in adult rats and rabbits demonstrating its potential as a post-coital contraceptive drug.
authors.affiliation: BIOQUAL Inc., 9600 Medical Center Drive, Rockville, MD 20850, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Hild
authors.forename: J R
authors.initials: JR
authors.lastname: Reel
authors.forename: L H
authors.initials: LH
authors.lastname: Hoffman
authors.forename: R P
authors.initials: RP
authors.lastname: Blye
mesh_terms: D000818:Animals; D003283:Contraceptives, Postcoital, Synthetic / Q000494:pharmacology*; D003307:Copulation; D005260:Female; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D009649:Norpregnadienes / Q000494:pharmacology*; D011247:Pregnancy; D011372:Progestins / Q000037:antagonists & inhibitors*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003283:Contraceptives, Postcoital, Synthetic; D005938:Glucocorticoids; D006727:Hormone Antagonists; D009649:Norpregnadienes; D011372:Progestins; D015735:Mifepristone; C094854:ulipristal