Human Reproduction, Vol. 15, No. 4, 822-829,
April 2000
© 2000 European Society of Human Reproduction and Embryology
CDB-2914: Anti-progestational/anti-glucocorticoid profile and post-coital anti-fertility activity in rats and rabbits*
1 BIOQUAL Inc., 9600 Medical Center Drive, Rockville, MD 20850, 2 Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN and 3 Contraception and Reproductive Health Branch, National Institute Child Health and Human Development, Rockville, MD, USA
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.
Key words: agonist/antagonist/anti-fertility/glucocorticoid/progestin
* A portion of this work was presented at the 29th Annual Meeting of the Society for the Study of Reproduction (1996) Abstract 310.
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