Puri C P, Patil R K, Kholkute S D, Elger W A, Swamy X R
Institute for Research in Reproduction (ICMR), Parel, Bombay, India.
Am J Obstet Gynecol. 1989 Jul;161(1):248-53. doi: 10.1016/0002-9378(89)90274-3.
The effects of a progesterone antagonist ZK 98.734 (lilopristone) on implantation, early pregnancy, and midpregnancy were studied in the common marmoset, Callithrix jacchus jacchus. Treatment (5 mg/da intramuscularly for 3 consecutive days) on day (n = 8) after the midcycle peak in estradiol levels in mated animals induced a premature drop in plasma progesterone levels and shortened the ovarian cycle length. Treatment on day 20 (n = 5) or day 40 (n = 5) induced a drop in progesterone levels and decidual collapse. In three animals treated on day 40, vaginal bleeding was observed within 46 hours of the initiation of treatment. Treatment on day 80 resulted in expulsion of the fetuses with a mean induction abortion interval of 39 hours (range, 20 to 48 hours). The progesterone antagonistic effects of ZK 98.734 could be a result of the decrease in progesterone synthesis by the corpus luteum and/or placenta in addition to the interference with the progesterone binding to its cellular receptors in the target organ. Our study suggests that ZK 98.734 has potential for fertility regulation. Clinical trials for postcoital contraception, induction of menstruation, and early abortifacient effects are warranted.
在普通狨猴(Callithrix jacchus jacchus)中研究了孕激素拮抗剂ZK 98.734(利洛司酮)对着床、早期妊娠和中期妊娠的影响。在交配动物雌二醇水平出现中期高峰后的第(n = 8)天进行治疗(连续3天,每天5 mg,肌肉注射),导致血浆孕激素水平过早下降,并缩短了卵巢周期长度。在第20天(n = 5)或第40天(n = 5)进行治疗,导致孕激素水平下降和蜕膜塌陷。在第40天接受治疗的3只动物中,在开始治疗后的46小时内观察到阴道出血。在第80天进行治疗导致胎儿排出,平均引产间隔为39小时(范围为20至48小时)。ZK 98.734的孕激素拮抗作用可能是黄体和/或胎盘孕激素合成减少的结果,此外还干扰了孕激素与其靶器官细胞受体的结合。我们的研究表明,ZK 98.734具有生育调节潜力。有必要进行性交后避孕、诱导月经和早期堕胎效果的临床试验。