POSTCOITAL USE OF ANORDRIN AND RU 486 FOR PREVENTION OF IMPLANTATION IN THE RAT

Because RU 486 synergizes with anordrin and its dihydroxylated metabolite to terminate established pregnancy in the rat and rabbit, the interactions of these agents were studied at two days postcoitally in the rat. RU 486 at a dose of 4 mg/kg did not prevent pregnancy when the animals were killed 12 days post insemination. A 2.5 mg/kg dose of anordrin prevented pregnancy in 14% of animals. By contrast, none of the animals became pregnant when treated with 2.5 mg/kg of anordiol. A non-effective dose of RU 486 (2 or 4 mg/kg) combined with a non-effective dose of anordrin (1.25 or 2.5 mg/kg) prevented pregnancy in all animals treated; there was no evidence of implantation sites or embryos when the animals were killed on day 12 post insemination. The same synergistic effect was observed when a small dose of RU 486 (e.g., 1 mg/kg) was combined with 0.6 mg/kg anordiol. To investigate the mechanism of pregnancy prevention, animals were treated two days postcoitally with 4 mg/kg of RU 486 plus 2.5 mg/kg of anordrin or 2 mg/kg of RU 486 plus 0.6 mg/kg of anordiol and were killed short intervals after treatment. These drugs had no effect by 6 h, but the numbers of embryos in oviducts were significantly reduced 12 h after treatment. By 24 h following treatment, no embryos were recovered from either the oviduct or the uterus. Progesterone and estradiol levels in serum collected 24 h after treatment were not significantly different from those of controls. These findings demonstrate that combinations of RU 486 plus anordrin or anordiol synergize to prevent pregnancy in the rat when administered postcoitally.