Duration of antiestrogenecity of compound CDRI-85/287: a new orally active nonsteroidal antiimplantation agent.

ABSTRACT

Duration of antiestrogenic and antiimplantation action of CDRI-85/287, (2-(4-(2-N-piperidino)ethoxy phenyl)-3-phenyl(2H)benzo(2)pyran), was studied in rat. Pretreatment of ovariectomized immature rats with this compound caused translocation of cytoplasmic estrogen receptor (ER) to the nucleus and a marked depletion of cytoplasmic ER pool resulting in a nonresponsive state of the uterus to subsequent estrogen administration until day 4. While in rats pretreated with estradiol, increased cytoplasmic ER level made the uterus responsive to a second injection of estrogen. In the delayed implantation model, 85/287 pretreated rats were given estrone on days 4, 5 or 6 post-antiestrogen treatment. No implantations were observed after estrone administration on day 4, but were present when estrone was given on days 5 or 6. Summation of these results suggests the duration of action of 85/287 to be 3-4 days in rat.