Win 32,729, a new, potent interceptive agent in rats and rhesus monkeys.
Win 32,729 [(2 alpha, 4 alpha, 5 alpha, 17 beta)-4,5-epoxy-17-hydroxy-4,17-dimethyl-3-oxoandrostane-2-carbonitrile] is an orally active interceptive agent in rats and rhesus monkeys (M mulatta). A single oral dose of 48 mg/kg terminated gestation when given on Day 10 of pregnancy. When given orally for up to 5 days to pregnant monkeys, it terminated pregnancy in 26 of 34 animals at a dose of 50 mg/monkey (ca 7 mg/kg), in 18 of 24 at a dose of 100 mg/monkey (ca 14 mg/kg) and in all 6 at 250 mg/monkey (ca 35 mg/kg). It did not inhibit ACTH-stimulated glucocorticoid production at 50 mg/monkey but did at a dose of 250 mg/monkey. This preferential gonadal inhibition was not evident in rodents. While in most cases five oral medications of 50-100 mg were required to terminate gestation in 50-day pregnant monkeys, a single subcutaneous medication with 250 mg was also effective, terminating pregnancy in 7 of 7 monkeys.
D000019:Abortifacient Agents; D000021:Abortifacient Agents, Steroidal; D000311:Adrenal Glands / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008251:Macaca / Q000502:physiology*; D008253:Macaca mulatta / Q000502:physiology*; D010053:Ovary / Q000187:drug effects; D011247:Pregnancy / Q000187:drug effects*; D011374:Progesterone / Q000097:blood / Q000494:pharmacology; D051381:Rats / Q000502:physiology*; D013256:Steroids / Q000037:antagonists & inhibitors; D013997:Time Factors
D000019:Abortifacient Agents; D000021:Abortifacient Agents, Steroidal; D013256:Steroids; D013196:Dihydrotestosterone; D011374:Progesterone; C033264:4,17-dimethyltrilostane; D000324:Adrenocorticotropic Hormone