Interceptive Activities of STS 557 in Rabbits, Mice and Rats¹)

Abstract

STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) is a interceptive agent in rabbits, mice and rats. In rats, it also shows post-implantational pregnancyterminating activity. In rabbits treated orally before mating or after ovulation for three consecutive days, it inhibited pregnancy largely at total doses of 0.08 mg/kg in the former and completely with 8.0 mg/kg in the latter case. A single subcutaneous dose of 40 mg/kg given on day 1 of pregnancy inhibited completely nidation in rats. In inhibition of pregnancy in rats could also be realized when the dose of 40 mg/kg was distributed on several days and given subcutaneously at daily doses of 5.0 mg/kg on days 1--8 of pregnancy, and even only daily doses of 2 mg STS 557/kg were needed in this respect, if animals which showed no living conceptuses were scored as "non-pregnant". STS 557 was effective in terminating pregnancy in rats, too, when given subcutaneously after implantation for 4 days at daily doses of 50 mg/kg, beginning on day 5 or on day 8 of pregnancy. The nidation inhibiting effects of STS 557 in rabbits treated pre-coitally, and in mice as well as in rats treated post-coitally were more marked than those of levonorgestrel. The interceptive and post-implantational inhibiting activity of STS 557 may be based on its antiprogestagenic properties. Luteolysis in the nidation phase can be excluded as shown by radioimmunoassay of progesterone in rats. The antigestagenic effects on the endometrium in rats were evident in the diamine oxidase assay. The acceleration of tubal egg transport, the morphological changes of the endometrium shown by scanning electron microscopy, and the effects on blastocyst transfer, all investigated in rats, suggest peripheral mechanisms of action.

The Effect of a Single Midcycle Administration of 0.5 or 2.0 mg Dienogest (17α-cyanomethyl- 17β-hydroxy-estra-4, 9-dien-3-one)on Pituitary and Ovarian Function - Investigation for the Use as a Postcoital Contraceptive1)

“…In order to minimize unwanted side-effects, the development of new oral active progestins for use in postcoital fertility control is necessary. In this respect dienogest is of interest for it shows postcoital antifertility action in rodents and baboons Strecke et al, 1983;. In baboons the effective dose of 0.4 mg produced no cycle disturbances .…”

“…In previous publications dienogest (STS 557, 17x-cyanomethyl-17ß-hydroxy-estra-4,9-dien-3-one, VEB Jenapharm, Jena/GDR) was characterized as a highly effective interceptive in rodents , Strecke et al, 1983. In addition, postcoital oral application of dienogest has good contraceptive action in baboons .…”

Effects of the New Progestagen STS 557 on the Biosynthesis of Steroids in Tissue Slices of the Human Ovary

“…In previous publications, STS 557 was characterized as a highly active progestagen with good antiprogestagenic properties in rabbits (Oettel and Kurischko, 1980;Stölzner et al, 1983) isornerase activity in tissue slices from a human ovary. x -X Controls (100%); .…”

“…STS 557 (17c-cyanomethyl-17ß-hydoxy-estra-4, 9-dien-3-one) was characterized as a highly active progestagen with good antiprogestagenic properties in rabbits (Oettel and Kurischko, 1980;Stölzner et al, 1983). Previous publications have shown that widely used orally active progestagens like D-norgestrel, norethisterone acetate and chiormadinone acetate as well as the antiandrogen cyproterone act directly on the steroid biosynthesis in the human ovary in vitro (Schürenkämper and Lisse, 1978;1975;1982).…”