Glucocorticoid receptor blockers

Molitch, Mark E.

doi:10.1007/s11102-022-01227-x

Cited by 15 publications

(5 citation statements)

References 12 publications

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“…The subjects that successfully completed the previous phase (N=52), underwent a 48h period of either a mifepristone (N=26, females=14) or a control immersion treatment (N=26, females=13) starting on the next day (day 4, 8a.m.). The duration of the immersion treatment is well within the half-life of mifepristone (84h, see Molitch, 2022) and was chosen as a compromise between a maximised exposure time and a limited confinement of the fish in a small space. Half of the females and half of the males were randomly assigned to one of the two treatments, in a way that ensured that the observer was blind to the treatments of the fish within each block.…”

Section: Experimental Phasesmentioning

confidence: 99%

“…Mifepristone is an antiprogestin and GR antagonist with several clinical applications (Spitz, 2003). At higher dosages it mainly acts as a GR antagonist (Alderman et al, 2012; Carbajal et al, 2023; Lawrence et al, 2017; Molitch, 2022; Oitzl and de Kloet, 1992; Ros et al, 2012; Veillette et al, 2007) with an affinity to GRs that is tenfold higher than that of cortisol (Molitch, 2022). In contrast, at lower dosages it mainly acts as an antiprogestin interacting with progesterone receptors (PRs) and as such, it is also used as a non-invasive method to terminate pregnancies (Blüthgen et al, 2013; Spitz et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Does the stress axis mediate behavioural flexibility in a social cichlid,Neolamprologus pulcher?

Fischer,

Ferlinc,

Hirschenhauser

et al. 2023

Preprint

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Behavioural flexibility plays a major role in the way animals cope with novel situations, and physiological stress responses are adaptive and highly efficient mechanisms to cope with unpredictable events. Previous studies investigating the role of stress responses in mediating behavioural flexibility were mostly done in laboratory rodents using stressors and cognitive challenges unrelated to the ecology of the species. To better understand how stress mediates behavioural flexibility in a natural context, direct manipulation of the stress response and cognitive tests in ecologically relevant contexts are needed. To this aim, we pharmacologically blocked glucocorticoid receptors (GR) in adult cichlid fish using a minimally invasive application of a GR antagonist. GRs blockade prevents the termination of the stress response, which we predicted to impair behavioural flexibility. After the application of the GR antagonist, we repeatedly exposed fish to a predator and tested their behavioural flexibility using a detour task, i.e. fish had to find a new, longer route to the shelter when the shortest route was blocked. While the latencies to find the shelter were not different between treatments, GR blocked fish showed more failed attempts during the detour tasks than control fish. Furthermore, reduced performance was accompanied by an increase of fear related behaviours. This suggests that blocking GRs plays an important role in determining perceived fear and resulted in an impaired behavioural flexibility. We confirm a causal role of terminating the stress response in mediating behavioural flexibility with potential consequences for an effective and adaptive coping with changing environments.

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Section: Experimental Phasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Does the stress axis mediate behavioural flexibility in a social cichlid,Neolamprologus pulcher?

Fischer,

Ferlinc,

Hirschenhauser

et al. 2023

Preprint

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show abstract

“…30,31 Mifepristone was also approved by the FDA in 2012 for the treatment of Cushing syndrome in patients that are not candidates for surgery or have not achieved remission after surgery, 32 and is currently the only glucocorticoid receptor antagonist approved for this condition. 33 The FDA approval for this use for mostly based on the SEISMIC (Study of the Efficacy and Safety of Mifepristone in the treatment of endogenous Cushing Syndrome) clinical trial, which showed that 60% of patients with hyperglycemia reached their glycemic endpoint, 38% of the patients had a decrease in their diastolic blood pressure, and 87% of patients had an improvement in clinical status. 33,34 The benefit of mifepristone in Cushing Syndrome is because of its ability to bind the glucocorticoid receptor, by an affinity about 18-times higher than that of cortisol, and block the activity of cortisol.…”

mentioning

confidence: 99%

“…33 The FDA approval for this use for mostly based on the SEISMIC (Study of the Efficacy and Safety of Mifepristone in the treatment of endogenous Cushing Syndrome) clinical trial, which showed that 60% of patients with hyperglycemia reached their glycemic endpoint, 38% of the patients had a decrease in their diastolic blood pressure, and 87% of patients had an improvement in clinical status. 33,34 The benefit of mifepristone in Cushing Syndrome is because of its ability to bind the glucocorticoid receptor, by an affinity about 18-times higher than that of cortisol, and block the activity of cortisol. 35 This application was first demonstrated in 1985, in a patient with Cushing syndrome as a result of ectopic ACTH secretion.…”

mentioning

confidence: 99%

Mifepristone: A Safe Method of Medical Abortion and Self-Managed Medical Abortion in the Post-Roe Era

Schmidt

Katz

Stein³

2022

American Journal of Therapeutics

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Background:The U.S. Supreme Court's Dobbs v. Jackson Women's Health Organization decision on June 24, 2022 effectively overturned federal constitutional protections for abortion that have existed since 1973 and returned jurisdiction to the states. Several states implemented abortion bans, some of which banned abortion after 6 weeks and others that permit abortion under limited exceptions, such as if the health or the life of the woman is in danger. Other states introduced bills that define life as beginning at fertilization. As a result of these new and proposed laws, the future availability of mifepristone, one of two drugs used for medical abortion in the United States, has become the topic of intense debate and speculation.Areas of Uncertainty:Although its safety and effectiveness has been confirmed by many studies, the use of mifepristone has been politicized regularly since its approval. Areas of future study include mifepristone for induction termination and fetal demise in the third trimester and the management of leiomyoma.Data Sources:PubMed, Society of Family Planning, American College of Obstetricians and Gynecologists, the World Health Organization.Therapeutic Advances:The use of no-touch medical abortion, which entails providing a medical abortion via a telehealth platform without a screening ultrasound or bloodwork, expanded during the COVID-19 pandemic, and studies have confirmed its safety. With the Dobbs decision, legal abortion will be less accessible and, consequently, self-managed abortion with mifepristone and misoprostol will become more prevalent.Conclusions:Mifepristone and misoprostol are extremely safe medications with many applications. In the current changing political climate, physicians and pregnancy-capable individuals must have access to these medications.

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“…Elevated salivary cortisol levels are the earliest reflection of disease recurrence. Medical treatment is increasingly being used [9][10][11][12], including preoperatively or as primary therapy. From no FDAapproved medication for CS in 2012, there are now four, with different mechanisms of action: mifepristone for hyperglycemia associated with CS, pasireotide and osilodrostat for CD and levoketoconazole for CS treatment;ketoconazole and metyrapone have been also recently approved in Europe.…”

mentioning

confidence: 99%

Special issue: Cushing's disease update

Fleseriu

2022

Pituitary

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Glucocorticoid receptor blockers

Cited by 15 publications

References 12 publications

Does the stress axis mediate behavioural flexibility in a social cichlid,Neolamprologus pulcher?

Does the stress axis mediate behavioural flexibility in a social cichlid,Neolamprologus pulcher?

Mifepristone: A Safe Method of Medical Abortion and Self-Managed Medical Abortion in the Post-Roe Era

Special issue: Cushing's disease update

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