Studies on the mechanisms of action of progesterone antagonists.
Antigestagens of RU-38.486-type were investigated in different pregnancy models reflecting either "endometrial" or "myometrial" effects. All antigestagens were found effective inhibitors of nidation in guinea pigs. This was evidence for a role of embryonic progesterone in the earliest events of nidation. No comparable inhibition could be obtained by ovariectomy. A more complex pharmacology was found around day 43 p.c. when the abortion was brought about by expulsion. RU-38.486 had marginal activity only. Antigestagens with reduced anti-glucocorticoid activity tended to induce abortions more effectively and faster. Some antigestagen-prostaglandin combinations were found of extreme abortifacient activity. Surprisingly it seemed that anti-glucocorticoid properties in addition to (or rather than) antigestagenic activities bring about this synergism with prostaglandin. The employed guinea pig model for pregnancy termination thus characterized two types of antigestagens: ideal ones for monotherapy or combined use with prostaglandin, respectively. Antigestagens induced a highly sensitive myometrium to prostaglandin-stimulation (Sulprostone) and a marked softening and dilatation of the cervix. Antigestagens perfectly prime the genital tract for oxytocic stimuli, they do not overcome the arrested uterine prostaglandin-secretion of the pregnant uterus at the same time.
D000021:Abortifacient Agents, Steroidal; D000818:Animals; D015232:Dinoprostone / Q000031:analogs & derivatives*; D010064:Embryo Implantation / Q000187:drug effects; D011464:Epoprostenol / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007743:Labor, Obstetric / Q000187:drug effects; D015735:Mifepristone; D011247:Pregnancy; D011374:Progesterone / Q000037:antagonists & inhibitors*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects
D000021:Abortifacient Agents, Steroidal; D004963:Estrenes; D011459:Prostaglandins E, Synthetic; D015735:Mifepristone; D011374:Progesterone; C016767:sulprostone; D011464:Epoprostenol; D015232:Dinoprostone