Antiovulatory and postcoital antifertility activity of the antiprogestin CDB-2914 when administered as single, multiple, or continuous doses to rats.
The present studies in rats were undertaken to investigate the potential of a new antiprogestin, CDB-2914, for use as an emergency postcoital contraceptive for women. When given orally at noon on the day of proestrus, both CDB-2914 and mifepristone displayed dose-dependent antiovulatory activity; however, CDB-2914 was about eight times more potent than mifepristone. Both antiprogestins were considerably less potent in blocking ovulation when injected subcutaneously. To evaluate antifertility activity during continuous low dose administration, rats were dosed orally with 0.5 mg of either CDB-2914 or mifepristone daily, commencing on the day of estrus and continuing for 24 days. Females were cohabited with proven fertile males on day 8 of treatment and were removed 1-3 days later after confirmed mating. The pregnancy rate was significantly reduced (p < 0.05) only in the CDB-2914-treated females; however, the mean number of normal implantation sites per pregnant rat was significantly reduced (p < 0.05) by mifepristone as compared with the vehicle control group. CDB-2914 was also found to prevent pregnancy when administered orally after mating from days 0-3 during tubal egg transport, or from days 4-6 during the pre- and peri-implantation periods. To determine the day of maximal sensitivity to CDB-2914, a single 2-mg dose per rat was given orally on days 0, 1, 2, 3, 4, or 5 postmating. This dose of CDB-2914 was without effect on pregnancy at days 0, 1, 2, or 3 postmating. In contrast, 2 mg CDB-2914 per rat was highly effective in blocking pregnancy when given on either day 4 or 5 postmating. Collectively, these data demonstrate that CDB-2914 is an orally active postcoital antifertility agent that is more potent than mifepristone in the rat. Hence, CDB-2914 may prove to be an effective emergency postcoital contraceptive in women.
BIOQUAL, Inc., Rockville, MD 20852-3336. jrreel@compuserve.com
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D000818:Animals; D003283:Contraceptives, Postcoital, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005298:Fertility / Q000187:drug effects; D015735:Mifepristone / Q000494:pharmacology; D009649:Norpregnadienes / Q000008:administration & dosage / Q000494:pharmacology*; D010060:Ovulation / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D003283:Contraceptives, Postcoital, Synthetic; D009649:Norpregnadienes; D015735:Mifepristone; C094854:ulipristal