CDB-2914: anti-progestational/anti-glucocorticoid profile and post-coital anti-fertility activity in rats and rabbits

Hum Reprod. 2000 Apr;15(4):822-9. doi: 10.1093/humrep/15.4.822.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Contraceptives, Postcoital, Synthetic / pharmacology*
  • Copulation
  • Female
  • Glucocorticoids / antagonists & inhibitors*
  • Hormone Antagonists / pharmacology
  • Male
  • Mifepristone / pharmacology
  • Norpregnadienes / pharmacology*
  • Pregnancy
  • Progestins / antagonists & inhibitors*
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Contraceptives, Postcoital, Synthetic
  • Glucocorticoids
  • Hormone Antagonists
  • Norpregnadienes
  • Progestins
  • Mifepristone
  • ulipristal