ArticleDrug and alcohol dependence2015
Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic-pituitary-adrenal axis activation.
Article in Drug and alcohol dependence, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03548714 (PT150), which is not on this map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
PT150 (Formerly ORG34517) as a Potential Treatment for Alcohol Dependence-Alcohol Interaction Study
Who cites it
12 citing papers in PubMed.
- A randomized trial of safety and pharmacodynamic interactions between a selective glucocorticoid receptor antagonist, PT150, and ethanol in healthy volunteers.Scientific reports · 2021Trial
- Double-blind, placebo-controlled trial of mifepristone on cognition and depression in alcohol dependence.Trials · 2020Trial
- Chronic administration of glucocorticoid receptor ligands increases anxiety-like behavior and selectively increase serotonin transporters in the ventral hippocampus.Brain research · 2023Article
- Effects of adolescent alcohol exposure via oral gavage on adult alcohol drinking and co-use of alcohol and nicotine in Sprague Dawley rats.Drug and alcohol dependence · 2022Article
- Effects of the glucocorticoid receptor antagonist PT150 on stress-induced fentanyl seeking in male and female rats.Psychopharmacology · 2021Article
- Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2.Cell cycle (Georgetown, Tex.) · 2020Article
- Repeated subcutaneous administration of PT150 has dose-dependent effects on sign tracking in male Japanese quail.Experimental and clinical psychopharmacology · 2019Article
- Methanol extract of semen Ziziphi Spinosae attenuates ethanol withdrawal anxiety by improving neuropeptide signaling in the central amygdala.BMC complementary and alternative medicine · 2019Article
- A glucocorticoid receptor antagonist reduces sign-tracking behavior in male Japanese quail.Experimental and clinical psychopharmacology · 2018Article
- Central Role of Glucocorticoid Receptors in Alzheimer's Disease and Depression.Frontiers in neuroscience · 2018Review
- Corticosterone enhances N-methyl-D-aspartate receptor signaling to promote isolated ventral tegmental area activity in a reconstituted mesolimbic dopamine pathway.Brain research bulletin · 2016Article
- Group 1 mGlu-family proteins promote neuroadaptation to ethanol and withdrawal-associated hippocampal damage.Drug and alcohol dependence · 2015Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
backgroundThe development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal.
methodsAdult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 11:00hours on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60mg/kg/i.g.) or a placebo and withdrawal was monitored.
resultsPeak BELs of 225.52mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g., aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects.
conclusionsThe present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence.
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