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Win 32,729,一种对大鼠和恒河猴有效的新型阻断剂。

Win 32,729, a new, potent interceptive agent in rats and rhesus monkeys.

作者信息

Creange J E, Anzalone A J, Potts G O, Schane H P

出版信息

Contraception. 1981 Sep;24(3):289-99. doi: 10.1016/0010-7824(81)90042-1.

Abstract

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.

摘要

孕三烯酮[(2α,4α,5α,17β)-4,5-环氧-17-羟基-4,17-二甲基-3-氧代雄烷-2-甲腈]在大鼠和恒河猴(食蟹猴)中是一种口服活性的避孕药物。在妊娠第10天给予48mg/kg的单次口服剂量可终止妊娠。当对怀孕的猴子口服给药长达5天时,剂量为50mg/猴(约7mg/kg)时,34只动物中有26只终止妊娠;剂量为100mg/猴(约14mg/kg)时,24只中有18只终止妊娠;剂量为250mg/猴(约35mg/kg)时,6只全部终止妊娠。在50mg/猴的剂量下,它不抑制促肾上腺皮质激素刺激的糖皮质激素生成,但在250mg/猴的剂量下则会抑制。这种对性腺的优先抑制在啮齿动物中并不明显。虽然在大多数情况下,需要对50天大的怀孕猴子口服5次50-100mg的药物才能终止妊娠,但单次皮下注射250mg也有效,7只猴子中有7只终止妊娠。

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