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Last update 08 May 2025

GR x SERT

Last update 08 May 2025

Basic Info

Related Targets

GRSERT

Drugs associated with GR x SERT

Paroxetine/Prednisolone

Target

GR x SERT

Mechanism

GR agonists [+1]

Active Org.-

Originator Org.

CombinatoRx, Inc.

Active Indication-

Inactive Indication

Inflammation [+1]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with GR x SERT

EUCTR2005-001440-23-SE

/ Not yet recruitingNot Applicable

A SINGLE CENTER, BLINDED, PLACEBO-CONTROLLED, RANDOMIZED STUDY OF THE EFFECT OF CRx-139 ON POCKET DEPTH AND INFLAMMATORY CYTOKINES COMPARED TO PLACEBO IN SUBJECTS WITH SEVERE ADULT PERIODONTITIS - CRx-139-PE

Start Date22 Sep 2005

Sponsor / Collaborator

CombinatoRx, Inc.

100 Clinical Results associated with GR x SERT

100 Translational Medicine associated with GR x SERT

0 Patents (Medical) associated with GR x SERT

106

Literatures (Medical) associated with GR x SERT

01 Apr 2025·Behavioural Pharmacology

The effect of Psilocybe cubensis alkaloids on depressive-like behavior in mice exposed to maternal separation with respect to hippocampal gene expression and DNA methylation of Slc6a4 and Nr3c1

Article

Author: Jasemi, Eghbal ; Amiri, Shayan ; Najafi, S. Mahmoud A. ; Razmi, Ali ; Vaseghi, Salar

Maternal separation as an early life stress can lead to long-lasting deleterious effects on cognitive and behavioral functions, and the mood state. On the other hand, Psilocybe cubensis (as one of the most well-known magic mushrooms) may be beneficial in the improvement or the treatment of neuropsychiatric disorders. In the present study, we aimed to investigate the effect of P. cubensis extract (PCE) on depressive-like and anxiety-like behaviors, and locomotor activity in mice exposed to early maternal separation. Also, we assessed the expression and methylation level of Slc6a4 and Nr3c1 in the hippocampus. Maternal separation was done in postnatal days (PNDs) 2–18. PCE was intraperitoneally injected at the dose of 20 mg/kg at PND 60, and our tests were done at days 1, 3, and 10, of administration. The results showed that maternal separation significantly induced depressive-like behavior in the forced swim test and anxiety-like behavior in the open field test (OFT). Also, maternal separation decreased locomotor activity in the OFT. In addition, maternal separation decreased the expression and increased the methylation level of both Slc6a4 and Nr3c1 in the hippocampus. However, PCE significantly reversed all these effects. In conclusion, it seems that P. cubensis affects serotonergic signaling via altering Slc6a4 expression and methylation level in the hippocampus of mice. The effect of P. cubensis on Nr3c1 expression and methylation level may also lead to alter the function of the hypothalamus-pituitary-adrenal axis and the stress response in mice exposed to maternal separation.

01 Mar 2025·Biological Psychiatry Global Open Science

Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric Population

Article

Author: Harker, Samantha A ; Lewis, Candace R ; Deoni, Sean C L ; Burton, Phoebe ; Spencer, Sophia ; Koinis-Mitchell, Daphne ; Hanson, Taena ; Braden, B Blair ; Beauchemin, Jennifer ; Mennenga, Sarah E ; D'Sa, Viren ; Barry, Fatoumata

BackgroundHippocampal volume increases throughout early development and is an important indicator of cognitive abilities and mental health. However, hippocampal development is highly vulnerable to exposures during development, as seen by smaller hippocampal volume and differential epigenetic programming in genes implicated in mental health. However, few studies have investigated hippocampal volume in relation to the peripheral epigenome across development, and even less is known about potential genetic moderators. Therefore, in this study, we explored relationships between hippocampal volume and peripheral DNA methylation of mental health-related genes, specifically NR3C1, FKBP5, and SLC6A4, throughout early development and whether these associations were moderated by age or genotype.MethodsBilateral hippocampal volume was computed from T2-weighted images through FreeSurfer, and DNA methylation was measured from saliva using the Illumina MethylationEPIC microarray in a pediatric population (N = 248, females = 112, mean_age = 5.13 years, SD_age = 3.60 years).ResultsMultiple linear regression and bootstrapping analyses revealed that DNA methylation of NR3C1, FKBP5, and SLC6A4 was associated with hippocampal volume and that these relationships were moderated by age and gene-specific variants.ConclusionsThese findings support the validity of peripheral DNA methylation profiles for indirectly assessing hippocampal volume and development and underscore the importance of genotype and age considerations in research. Therefore, peripheral epigenetic profiles may be a promising avenue for investigating the impacts of early-life stress on brain structure and subsequent mental health outcomes.

01 Mar 2025·Journal of Neurophysiology

On the role of epigenetic modifications of HPA axis in posttraumatic stress disorder and resilience

Review

Author: Iqbal, Emann ; Khan, Zainab ; Zaidi, Mukarram ; Yusuf, Kamran ; Syed, Naweed I. ; Tanweer, Mohammad S. ; Hassan, Hadi ; Messiri, Nour El ; Sadia, Syeda R. ; Taj, Moizzuddin ; Zaidi, Umar

Stress is a fundamental adaptive response that invokes amygdala and hypothalamus-pituitary-adrenal (HPA) axis along with other brain regions. Extreme or chronic stress, however, can result in a multitude of neuropsychiatric disorders, including anxiety, paranoia, bipolar disorder (BP), major depressive disorder (MDD), and posttraumatic stress disorder (PTSD). Despite widespread exposure to trauma (70.4%), the incidence of PTSD is relatively low (6.8%), suggesting that either individual susceptibility or adaptability driven by epigenetic and genetic mechanisms are likely at play. PTSD takes hold from exposure to traumatic events, such as death threats or severe abuse, with its severity being impacted by the magnitude of trauma, its frequency, and the nature. This comprehensive review examines how traumatic experiences and epigenetic modifications in hypothalamic-pituitary axis (HPA), such as DNA methylation, histone modifications, noncoding RNAs, and chromatin remodeling, are transmitted across generations, and impact genes such as FKBP prolyl isomerase 5 ( FKBP5), nuclear receptor subfamily 3 group C member 1 ( NR3C1), brain-derived neurotrophic factor ( BDNF), and solute carrier family 6 member 4 ( SLC6A4). It also provides a comprehensive overview on trauma reversal, resilience mechanisms, and pro-resilience factors such as histone acetyltransferases (HATs)/histone deacetylases (HDACs) ratio, dehydroepiandrosterone (DHEA)/cortisol ratio, testosterone levels, and neuropeptide Y, thus highlighting potential therapeutic approaches for trauma-related disorders. The studies highlighted here underscore the narrative, for the first time, that the examination and treatment of PTSD and other depressive disorders must invoke a multitude of approaches to seek out the most effective and personalized strategies. We also hope that the discussion emanating from this review will also inform government policies directed toward intergenerational trauma and PTSD.

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