[Mifepristone--a controversial drug with great potential]. / Mifepriston--et kontroversielt legemiddel med stort potensial.

BACKGROUND: Antiprogestins, agents that inhibit the action of progesterone, are among the most controversial and yet the more interesting therapeutic compounds developed over the past 20 years. MATERIAL AND METHODS: We present a review of the literature identified through limited searches on Medline, Cochrane and the Internet, with a discussion of the biological, clinical, political and ethical aspects of this important drug. RESULTS: The first effective antiprogestin in clinical use was mifepristone (also known as RU 486). This agent provides the most effective and safest means of medical abortion. It may also be used as a contraceptive and delivery-inducing agent and in the treatment of spontaneous abortion, ectopic pregnancies, leiomyoma, endometriosis, intrauterine fetal death, Cushing's syndrome and progesterone-dependent malignancies. INTERPRETATION: The introduction of mifepristone as an abortion-inducing agent has created intense political, ethical and moral controversies which have delayed clinical investigations and evaluations for potential expanded use.

History and perspectives of antiprogestins from the chemist's point of view.

The discovery of RU486 and its potent activity as an antiglucocorticoid and antiprogestin brought the long story on steroid hormones and antihormones to its logical conclusion. Even though scattered improvements are still possible, the armamentarium of the steroid endocrinologist is by now complete. Like any successful drug, RU486 has become the prototype of a number of analogues which are claimed to be either more active or more dissociated. The literature (mainly patients) has been searched for available data on abortive activities, and some as yet unpublished results on RU compounds have been included. It appears that a number of compounds are both more active than RU486 on a dose basis in animal studies and more dissociated in relation to a possible antiglucocorticoid activity. In addition, hydrosoluble compounds suitable for i.v. injection are available for possible development. In a longer term perspective, it cannot be excluded that potential non-steroidal antiprogestins could present additional advantages over steroidal compounds, in particular improved receptor specificity and/or reduced susceptibility to receptor mutation.

PIP: The discovery of RU-486 and its potent activity as an antiglucocorticoid and antiprogestin have brought the protracted story on steroid hormones and antihormones to a logical conclusion. For each of the five traditional classes of steroid hormones, estrogens, androgens, progestins, glucocorticoids, and mineralcorticoids, potent agonists and antagonists are available. The armamentarium of the steroid endocrinologist is therefore complete although scattered improvements do remain possible. RU-486 has already become the prototype of a number of analogs claimed to be either more active or more dissociated. The authors searched the literature for available data on abortive activities, including some as yet unpublished results on RU compounds. It appears that a number of compounds are both more active than RU-486 on a dose basis in animal studies and more dissociated in relation to a possible antiglucocorticoid activity. Moreover, hydrosoluble compounds suitable for IV injection are available for possible development. Over the long-term, it is possible that nonsteroidal antiprogestins may present additional advantages over steroidal compounds, in particular improved receptor specificity and/or reduced susceptibility to receptor mutation.