ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
GR3027 antagonizes GABAA receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 74 citations in OpenAlex.
- GR3027 reversal of neurosteroid-induced, GABA-A receptor-mediated inhibition of human brain function: an allopregnanolone challenge study.Psychopharmacology · 2018Trial
- Minimal Hepatic Encephalopathy: A Narrative Review.Cureus · 2026Review
- Advances in understanding, diagnosing, and treating hepatic encephalopathy: from epidemiology to emerging therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Hyperammonemia reduces the populations of beneficial lactobacilli and bifidobacteria, disrupting the metabolic balance of the gut microbiome in rats.Frontiers in microbiology · 2026Article
- Golexanolone Attenuates Neuroinflammation, Fatigue, and Cognitive and Motor Impairment in Diverse Neuroinflammatory Disorders.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Hepatic encephalopathy in cirrhosis: therapies and developments.Metabolic brain disease · 2025Review
- Golexanolone affords sustained microglia and astrocytes activation improvement in a rat model of Parkinson's disease.Frontiers in immunology · 2025Article
- Extracellular vesicles from mesenchymal stem cells improve neuroinflammation and neurotransmission in hippocampus and cognitive impairment in rats with mild liver damage and minimal hepatic encephalopathy.Stem cell research & therapy · 2024Article
- Role of peripheral inflammation in minimal hepatic encephalopathy.Metabolic brain disease · 2024Review
- Hepatic encephalopathy as a result of ammonia-induced increase in GABAergic tone with secondary reduced brain energy metabolism.Metabolic brain disease · 2024Review
- Preface for the Vicente Felipo Honorary Issue of Neurochemical Research.Neurochemical research · 2024Article
- Golexanolone reduces glial activation in the striatum and improves non-motor and some motor alterations in a rat model of Parkinson's disease.Frontiers in aging neuroscience · 2024Article
- Neuroinflammation alters GABAergic neurotransmission in hyperammonemia and hepatic encephalopathy, leading to motor incoordination. Mechanisms and therapeutic implications.Frontiers in pharmacology · 2024Review
- The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary Study.International journal of molecular sciences · 2023Article
- Extra-Synaptic GABABiomolecules · 2023Article
- Effects of oxidative stress on hepatic encephalopathy pathogenesis in mice.Nature communications · 2023Article
- Isoallopregnanolone Inhibits Estrus Cycle-Dependent Aggressive Behavior.Biomolecules · 2023Article
- Extracellular vesicles from mesenchymal stem cells reduce neuroinflammation in hippocampus and restore cognitive function in hyperammonemic rats.Journal of neuroinflammation · 2023Article
- Golexanolone, a GABACNS neuroscience & therapeutics · 2022Article
- Enhanced BDNF and TrkB Activation Enhance GABA Neurotransmission in Cerebellum in Hyperammonemia.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatic encephalopathy (HE) is one of the primary complications of liver cirrhosis. Current treatments for HE, mainly directed to reduction of ammonia levels, are not effective enough because they cannot completely eliminate hyperammonemia and inflammation, which induce the neurological alterations. Studies in animal models show that overactivation of GABAA receptors is involved in cognitive and motor impairment in HE and that reducing this activation restores these functions. We have developed a new compound, GR3027, that selectively antagonizes the enhanced activation of GABAA receptors by neurosteroids such as allopregnanolone and 3α,21-dihydroxy-5α-pregnan-20-one (THDOC). This work aimed to assess whether GR3027 improves motor incoordination, spatial learning, and circadian rhythms of activity in rats with HE. GR3027 was administered subcutaneously to two main models of HE: rats with chronic hyperammonemia due to ammonia feeding and rats with portacaval shunts (PCS). Motor coordination was assessed in beam walking and spatial learning and memory in the Morris water maze and the radial maze. Circadian rhythms of ambulatory and vertical activity were also assessed. In both hyperammonemic and PCS rats, GR3027 restores motor coordination, spatial memory in the Morris water maze, and spatial learning in the radial maze. GR3027 also partially restores circadian rhythms of ambulatory and vertical activity in PCS rats. GR3027 is a novel approach to treatment of HE that would normalize neurological functions altered because of enhanced GABAergic tone, affording more complete normalization of cognitive and motor function than current treatments for HE.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.