Pharmacodynamics<unk>  is a steroidal antiprogestogen (IC50 = 0.025 nM for the PR), as well as an antiglucocorticoid (IC50 = 2.2 nM for the GR) and antiandrogen (IC50 = 10 nM for the AR) to a much lesser extent. It antagonizes cortisol action competitively at the receptor level. In the presence of progesterone,<unk>  acts as a competitive progesterone receptor antagonist (in the absence of progesterone,<unk>  acts as a partial agonist).<unk>  is a 19-nor steroid with a bulky p-(dimethylamino) phenyl substituent above the plane of the molecule at the 11β-position responsible for inducing or stabilizing an inactive receptor conformation and a hydrophobic 1-propynyl substituent below the plane of the molecule at the 17α-position that increases its progesterone receptor binding affinity. In addition to being an antiprogestogen,<unk>  is also an antiglucocorticoid and a weak antiandrogen.<unk> 's relative binding affinity at the progesterone receptor is more than twice that of progesterone, its relative binding affinity at the glucocorticoid receptor is more than three times that of dexamethasone and more than ten times that of cortisol. Its relative binding affinity at the androgen receptor is less than one-third that of testosterone, and it does not bind to the estrogen receptor or the mineralocorticoid receptor.<unk>  as a regular contraceptive at 2 mg daily prevents ovulation (1 mg daily does not). A single preovulatory 10-mg dose of<unk>  delays ovulation by three to four days and is as effective an emergency contraceptive as a single 1.5-mg dose of the progestin levonorgestrel. In women,<unk>  at doses greater or equal to 1 mg/kg antagonizes the endometrial and myometrial effects of progesterone. In humans, an antiglucocorticoid effect of<unk>  is manifested at doses greater or equal to 4.5 mg/kg by a compensatory increase in ACTH and cortisol. In animals, a weak antiandrogenic effect is seen with prolonged administration of very high doses of 10 to 100 mg/kg. In medical abortion regimens,<unk>  blockade of progesterone receptors directly causes endometrial decidual degeneration, cervical softening and dilatation, release of endogenous prostaglandins, and an increase in the sensitivity of the myometrium to the contractile effects of prostaglandins.<unk> -induced decidual breakdown indirectly leads to trophoblast detachment, resulting in decreased syncytiotrophoblast production of hCG, which in turn causes decreased production of progesterone by the corpus luteum (pregnancy is dependent on progesterone production by the corpus luteum through the first nine weeks of gestation—until placental progesterone production has increased enough to take the place of corpus luteum progesterone production). When followed sequentially by a prostaglandin,<unk>  200 mg is (100 mg may be, but 50 mg is not) as effective as 600 mg in producing a medical abortion. 'Contragestion' is a term promoted by Étienne-Émile Baulieu in the context of his advocacy of<unk> , defining it as inclusive of some hypothesized mechanisms of action of some contraceptives and those of<unk>  to induce abortion. adj. Capable of preventing gestation, either by preventing implantation or by causing the uterine lining to shed after implantation. —n. A contragestive drug or agent.Also contragestant, abortion pill. A substance called<unk> , or RU-486, which was developed by Dr. Etienne Baulieu and the Roussel-Uclaf company. The contragestive blocks progesterone receptors in the endometrium (uterine lining), preventing its buildup by progesterone; hence the uterus cannot sustain a pregnancy. It does not prevent fertilization or implantation, so technically it is an ABORTIFACIENT rather than a contraceptive. Baulieu's definition of a 'contragestive' included any birth control method that could possibly act after fertilization and before nine-weeks gestational age. Pharmacokinetics The elimination half-life is complex; according to the label: "After a distribution phase, elimination is at first slow, the concentration decreasing by a half between about 12 and 72 hours, and then more rapid, giving an elimination half-life of 18 hours. With radio receptor assay techniques, the terminal half-life is of up to 90 hours, including all metabolites of<unk>  able to bind to progesterone receptors." Metapristone is the major metabolite of<unk> .
Mifepristone
Metapristone
Telapristone
Ethinylestradiol sulfonate
Promegestone
Dydrogesterone
Aminoglutethimide
Formestane