Mifepristone

Abstract

Mifepristone is a potent oral antiprogestogen which acts at the level of the receptor, having a high affinity for the progesterone receptor. Most of the clinical trials have studied its efficacy in the termination of early pregnancy when used in conjunction with a low dosage of a prostaglandin analogue. In these studies, mifepristone 100 to 600mg administered as a single dose or over 3 or 4 days, 36 to 48 hours before a prostaglandin analogue given vaginally, intramuscularly or orally, induced complete abortion in about 95% of women. Used alone, mifepristone is an effective cervical priming agent prior to termination of first trimester pregnancy by vacuum aspiration, and facilitates termination of second trimester pregnancy by prostaglandin by reducing the interval between the start of prostaglandin treatment and termination, the cumulative prostaglandin dosage, and the adverse effects associated with these drugs. Mifepristone can also be used to induce labour in cases of intrauterine fetal death. Mifepristone has been shown to be an effective postcoital contraceptive with a likely emergency role, since its repeated use modifies the menstrual cycle. Pilot studies have been performed in unresectable meningioma and metastatic breast cancer, and in Cushing's syndrome. Mifepristone is generally well tolerated, and thus is an effective, appropriate, medical alternative to surgical termination of early pregnancy. It has as yet unexplored potential as a postcoital contraceptive and in oncology.

Receptor-Independent Activation of GABAergic Neurotransmission and Receptor-Dependent Nontranscriptional Activation of Phosphatidylinositol 3-kinase/Protein Kinase Akt Pathway in Short-Term Cardiovascular Actions of Dexamethasone at the Nucleus Tractus Solitarii of the Rat

“…Activation of type II, but not type I, glucocorticoid receptors contributes to hypertension induced by the agonists (Clapham and Turner, 1997). RU486 is a type II glucocorticoid receptor antagonist that does not bind to type I mineralocorticoid receptors or aldosterone receptors (Brogden et al, 1993). We also recognize that our results showed that GABA A or GABA B receptor antagonist by itself evoked hypotension and bradycardia.…”

“…These coordinates were selected to cover subdivisions of NTS in which functionally identified barosensitive neurons reside (Chan and Sawchenko, 1998). Test agents used included a synthetic glucocorticoid, Dex (Sigma-Aldrich, St. Louis, MO); a selective glucocorticoid type II receptor antagonist (Clapham and Turner, 1997;Limbourg et al, 2002), mifepristone (RU486; SigmaAldrich), that does not bind to the type I mineralocorticoid receptor or to aldosterone receptors (Brogden et al, 1993); a selective GABA A receptor antagonist (Galvez-Ruano et al, 1995), bicuculline methiodine (Sigma-Aldrich); a GABA B receptor antagonist (Al-Dahan et al, 1990), 2-hydroxy saclofen (2-OH saclofen; Sigma-Aldrich); a nonselective nitric-oxide synthase (NOS) inhibitor (Reif and McCreedy, 1995), N G -monomethyl-L-arginine acetate (L-NMMA; SigmaAldrich); a PI3K inhibitor (Vlahos et al, 1994), LY294002 (Calbiochem, San Diego, CA); and an RNA synthesis inhibitor , actinomycin D (AMD; Calbiochem). The dose and treatment scheme were adopted from previous reports (Clapham and Turner, 1997;Ouyang and Wang, 2000;Hafezi-Moghadam et al, 2002;Limbourg et al, 2002;Moreno et al, 2002;Chan et al, 2003), which used the same test agents for the same purpose as in this study.…”

A regulatory system for use in gene transfer.

“…These side effects are mostly due to the antiglucocorticoid activity at this high dosage (31). Because RU 486 is used as an agonist in this gene-switch system, we believe that there will be no significant antiglucocorticoid or other deleterious effects at this low dosage in animals or in humans.…”

Adenovirus-mediated regulable target gene expression in vivo

“…The doses of mifepristone needed for induction in our regulatory system (0.1-0.5 mg͞kg) is far below levels at which mifepristone is used as an antiprogestin (10 mg͞kg) together with prostaglandin to terminate pregnancy. Administration of mifepristone at levels much higher than those necessary for transgene induction in our regulatory system have been administered safely to patients on a daily basis to treat different diseases (21,22). Thus, it is likely that mifepristone, at this low concentration, can serve as a potent inducer for human gene therapy, even for a prolonged period of time.…”