Pharmacological Profile of RU 486 in Animals

  • D. Philibert
  • M. Moguilewsky
  • I. Mary
  • D. Lecaque
  • C. Tournemine
  • J. Secchi
  • R. Deraedt
Part of the Reproductive Biology book series (RBIO)


RU 486 is an original multifaceted antihormone. It appears to be a potent progestin and glucocorticoid antagonist while exhibiting no agonistic effect, even at very high doses. Thus, according to the bioassay used, RU 486 administered orally at doses between 3 and 20 mg/kg completely inhibits the effect of exogenous progesterone on the endometrial proliferation in rabbits, on the volume density of uterine gland cell mitochondria, on the deciduomata formation and on the maintenance of pregnancy in ovariectomized rats. Furthermore, it proves to be antinidatory and abortive in rats and mice. In cycling monkeys it induces menstruation when administered during the mid-luteal phase.

Acting as an antiglucocorticoid component, RU 486 effectively antagonizes, at 10M−6, dexamethasone’s effect on uridine incorporation into rat thymocytes RNA and on ACTH secretion from rat pituitary cells. In vivo (at a dose of 10 mg/kg to adrenalectomized rats) it fully prevents the thymolytic effect of corticosterone and dexamethasone; it also completely blocks urinary volume increase and potassium excretion induced by dexamethasone. In this latter test, its antiglucocorticoid activity is rapidly and fully reversed by increasing doses of dexamethasone. Using a perifusion technique, we observe that RU 486 does not inhibit corticosterone biosynthesis in rat adrenal cells stimulated by ACTH. The compound also possesses a moderate antiandrogenic activity on seminal vesicles and prostate weights, about 20 times weaker than its two other antagonist properties (evaluated in rats). In various species (rats, rabbits and mice) it exhibits a slight uterotrophic activity, approximately 10,000 times weaker than that of estradiol; but, unlike estrogens, it fails to induce estrus in ovariectomized rats given up to 300 mg/kg. When RU 486 is administered chronically for 15 days in adult female rats, it displays no antiovulatory activity; on the contrary, it provokes dose-dependent increases in serum LH and progesterone levels and ovarian weight.


Seminal Vesicle Testosterone Propionate Thymus Weight Uridine Incorporation Immature Rabbit 
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Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • D. Philibert
    • 1
  • M. Moguilewsky
    • 1
  • I. Mary
    • 1
  • D. Lecaque
    • 1
  • C. Tournemine
    • 1
  • J. Secchi
    • 1
  • R. Deraedt
    • 1
  1. 1.Centre de Recherches Roussel UclafRomainvilleFrance

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