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Psychoneuroendocrinology Mar 2021Glucocorticoid receptor (GR) antagonism is a promising new treatment for cognitive dysfunction in psychiatric disorders but the effects of GR antagonism on cognition...
Glucocorticoid receptor (GR) antagonism is a promising new treatment for cognitive dysfunction in psychiatric disorders but the effects of GR antagonism on cognition related brain activity is poorly understood. This study examines the effects of the GR and progesterone receptor antagonist mifepristone on the neural correlates of visuospatial learning and working memory in healthy male participants. The study used a pharmacological functional magnetic resonance imaging (fMRI) design to determine mifepristone effects on visuospatial paired associates learning (vPAL) and n-back working memory (WM) fMRI task related brain activations. 20 right-handed healthy male participants received 600 mg mifepristone or placebo on two separate imaging days and each participant performed fMRI tasks four hours later. The effect of mifepristone on task related brain activations was determined using Region of Interest (ROI) fMRI analyses and an exploratory whole brain voxel-wise fMRI task analyses was also conducted. The vPAL task ROI analysis found that mifepristone administration was significantly associated with decreased fusiform cortex activations in first and second encoding blocks (p = 0.007, p = 0.04) and decreased angular and precuneal cortices activations in the first recall block (p = 0.01, p = 0.02). There were no significant differences in fMRI brain activations associated with mifepristone administration in the n-back task ROI's (all p > 0.05). Mifepristone administration did not significantly affect fMRI brain activations in the whole brain voxel-wise analyses for both tasks. N-back and vPAL task reaction times and accuracy were similar in both mifepristone and placebo conditions (all p > 0.05). Our finding of decreased fusiform, angular and precuneal vPAL task related brain activity associated with mifepristone administration for the same behavioural performance as found in the placebo condition may represent improved efficiency of visuospatial memory encoding and recall. These findings provide evidence that mifepristone may enhance the efficiency of human visuospatial memory and calls for further studies in patient populations using an fMRI approach to provide proof of concept for new treatments.
Topics: Brain; Brain Mapping; Humans; Magnetic Resonance Imaging; Male; Memory, Short-Term; Mental Recall; Mifepristone
PubMed: 33418240
DOI: 10.1016/j.psyneuen.2020.105116 -
BMJ (Clinical Research Ed.) Apr 2023
Topics: Humans; Female; Pregnancy; Mifepristone; Abortion, Induced; Misoprostol
PubMed: 37072149
DOI: 10.1136/bmj.p864 -
Gynecological Endocrinology : the... Dec 2006Mifepristone is a progesterone antagonist that has been studied for a number of clinical applications. It is a well-known abortifacient that is effective for both first-... (Review)
Review
Mifepristone is a progesterone antagonist that has been studied for a number of clinical applications. It is a well-known abortifacient that is effective for both first- and second-trimester medical abortion when used with a prostaglandin analog. It is also an effective cervical priming agent that can be used to soften the cervix before surgical evacuation. Its clinical efficacy as an emergency contraception has been proven. Other applications including treatment for fibroids, endometriosis and various cancers have been explored. However, its association with abortion limits the applications of mifepristone in many of these areas.
Topics: Abortifacient Agents, Steroidal; Abortion, Induced; Abortion, Spontaneous; Contraceptive Agents; Female; Genital Diseases, Female; Humans; Mifepristone; Pregnancy
PubMed: 17162706
DOI: 10.1080/09513590601005946 -
Mifepristone: pharmacology and clinical impact in reproductive medicine, endocrinology and oncology.Expert Opinion on Pharmacotherapy Feb 2010Mifepristone is a synthetic selective progesterone-receptor modulator (SPRM) that is widely used around the globe in the field of reproductive medicine. At present... (Review)
Review
IMPORTANCE OF THE FIELD
Mifepristone is a synthetic selective progesterone-receptor modulator (SPRM) that is widely used around the globe in the field of reproductive medicine. At present mifepristone is approved in a number of countries for early termination of pregnancy (TOP), cervical dilatation before surgical TOP, and management of early embryonic loss or fetal death. A number of new clinical applications are being developed in gynecology, endocrinology and oncology. Mifepristone has also served as an invaluable tool in the study of steroid hormone biology.
AREAS COVERED IN THIS REVIEW
Current indications for mifepristone are reviewed. New applications for mifepristone under clinical investigation are discussed. In addition, the unique molecular and cellular effects of mifepristone are described.
WHAT THE READER WILL GAIN
The reader will understand the mechanisms of action of mifepristone and the underlying steroid hormone biology. The reader will know the approved clinical indications for mifepristone and appreciate the ongoing basic and clinical research into new applications.
TAKE HOME MESSAGE
Mifepristone is the first-discovered and still most widely used antiprogestin. It has several indications in reproductive medicine and is under investigation for a variety of potential applications in other fields of medicine. The molecular and cellular effects of mifepristone illuminate important aspects of steroid hormone biology.
Topics: Abortifacient Agents, Steroidal; Drug Approval; Drug Delivery Systems; Drug Design; Endocrinology; Female; Humans; Medical Oncology; Mifepristone; Pregnancy; Pregnancy Complications, Neoplastic; Reproductive Medicine; Uterine Neoplasms
PubMed: 20102310
DOI: 10.1517/14656560903535880 -
Journal of the Indian Medical... Jan 2014The first clinically available antiprogestin, mifepristone has generated immense interest in the research community since its' discovery in 1980. Mifepristone is a... (Review)
Review
The first clinically available antiprogestin, mifepristone has generated immense interest in the research community since its' discovery in 1980. Mifepristone is a synthetic orally active steroid with potent antiglucocorticoid, antiprogestogen and a weak anti-androgen activity, used primarily for termination of pregnancy. It acts as a competitive receptor antagonist at the progesterone receptor in the presence of progesterone, and acts as a partial agonist in the absence of progesterone. Extensive research has been carried out regarding its' antiprogestogen activity for use in medical abortion. Lately other medical uses of mifepristone are being explored like for induction of labour in late preg- nancy, as oestrogen free oral contraceptive and for treatment of endometriosis, uterine fibroids, ovarian cancer, prostate cancer, meningiomas, Cushing's syndrome and major psychotic depression.
Topics: Abortifacient Agents, Steroidal; Female; Humans; Male; Mifepristone
PubMed: 25935948
DOI: No ID Found -
Clinical Obstetrics and Gynecology Jun 1996Mifepristone is a potent antagonist of glucocorticoid and progesterone receptors. It is the only drug administered to humans with these actions. Exploration of... (Review)
Review
Mifepristone is a potent antagonist of glucocorticoid and progesterone receptors. It is the only drug administered to humans with these actions. Exploration of mifepristone in the treatment of Cushing's syndrome is in its infancy. The cases reviewed in this report comprise the entire medical literature. Development and availability of mifepristone has been severely restricted because of controversy surrounding its ability to function as an "abortion pill." As the political controversy abates, increasing studies of this drug may be anticipated in patients with glucocorticoid excess. Although the authors have highlighted therapeutic trials with the drug, they also note that diagnostic uses in cases of glucocorticoid excess may be of interest. Some cases of endogenous Cushing's syndrome are difficult to diagnosis and a glucocorticoid antagonist may be as useful as a glucocorticoid agonist (such as dexamethasone) in the dynamic evaluation of glandular function. In particular, mifepristone might be useful in distinguishing pituitary from occult ectopic ACTH-secreting tumors. One of the primary problems surrounding the use of mifepristone in cases of Cushing's syndrome is the long half-life of the drug and the necessity to titrate doses carefully in a manner that avoids signs and symptoms of glucocorticoid deficiency. Biochemical markers reflecting the "glucocorticoid status" of a patient would be useful for dose adjustment and monitoring and would improve the risk to benefit ratio for mifepristone treatment of Cushing's syndrome.
Topics: Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Glucocorticoids; Hormone Antagonists; Humans; Male; Mifepristone
PubMed: 8734015
DOI: 10.1097/00003081-199606000-00024 -
The New England Journal of Medicine Aug 1993
Review
Topics: Abortion, Induced; Animals; Endometrium; Female; Glucocorticoids; Humans; Mifepristone; Pregnancy; Progestins; Prostaglandins; Uterus
PubMed: 8326975
DOI: 10.1056/NEJM199308053290607 -
Lancet (London, England) Nov 1991
Topics: Abnormalities, Drug-Induced; Abortion, Induced; Female; Humans; Mifepristone; Pregnancy
PubMed: 1682707
DOI: 10.1016/0140-6736(91)92629-g -
The Annals of Pharmacotherapy Sep 2005To explain the role of mifepristone in medical abortions that results in fulminant and lethal septic shock due to Clostridium sordellii. (Review)
Review
OBJECTIVE
To explain the role of mifepristone in medical abortions that results in fulminant and lethal septic shock due to Clostridium sordellii.
DATA SOURCES
MEDLINE, PubMed, and Google Scholar databases were searched (1984-March 2005). Key search terms were mifepristone, RU38486, RU486, Mifeprex, medical abortion, septic shock, innate immune system, cytokines, and Clostridium sordellii.
STUDY SELECTION AND DATA EXTRACTION
All articles identified from the data sources were evaluated and all information deemed relevant was included for the information related to the development of the understanding of the pathophysiology of mifepristone-induced septic shock due to C. sordellii.
DATA SYNTHESIS
The mechanisms of action of mifepristone were incorporated into the pathophysiology of septic shock due to C. sordellii. Mifepristone, by blocking both progesterone and glucocorticoid receptors, interferes with the controlled release and functioning of cortisol and cytokines. Failure of physiologically controlled cortisol and cytokine responses results in an impaired innate immune system that results in disintegration of the body's defense system necessary to prevent the endometrial spread of C. sordellii infection. The abnormal cortisol and cytokine responses due to mifepristone coupled to the release of potent exotoxins and an endotoxin from C. sordellii are the major contributors to the rapid development of lethal septic shock.
CONCLUSIONS
Theoretically, it appears that the mechanisms of mifepristone action favor the development of infection that leads to septic shock and intensifies the actions of multiple inflammatory cytokines, resulting in fulminant, lethal septic shock.
Topics: Abortifacient Agents; Abortion, Septic; Clostridium Infections; Cytokines; Female; Humans; Immune System; Immunity, Innate; Mifepristone; Pregnancy; Receptors, Glucocorticoid; Shock, Septic
PubMed: 16046483
DOI: 10.1345/aph.1G189 -
The Medical Letter on Drugs and... Jan 2022
Topics: Abortifacient Agents, Steroidal; Abortion, Induced; Administration, Oral; Community Pharmacy Services; Female; Humans; Mifepristone; Patient Safety; Postal Service; Pregnancy; Risk Evaluation and Mitigation; Tablets; Treatment Outcome
PubMed: 35134042
DOI: No ID Found