ArticleCellular and molecular gastroenterology and hepatology2026
Development of a Novel Benzodiazepine to Delineate Peripheral GABA-A Signaling Mechanisms in Visceral Pain Syndromes.
Article in Cellular and molecular gastroenterology and hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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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.
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Who cites it
1 citing paper in PubMed.
- Master of innovation: unlocking creativity in the development of novel solutions from interventional endoscopy to neurogastroenterology.iGIE : innovation, investigation and insights · 2025Article
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Authors and funding
13 authors.
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No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsVisceral pain is a cardinal symptom of many disorders affecting the gut and other abdominal organs. Modulators of gamma-aminobutyric acid (GABA) such as benzodiazepines may attenuate such pain but the specific contribution of peripheral GABA-A receptors (GABRAs) remains unclear as current agonists have prominent central effects.
methodsUsing medicinal chemistry optimization of the benzodiazepine scaffold, we developed a novel and potent positive allosteric modulator (PAM), LI-633, with no significant central nervous system (CNS) penetration.
resultsThe locomotor activity of rats placed in an open field was unchanged with LI-633 at doses up to 30 mg/kg, confirming its lack of a CNS effect. LI-633 produced robust potentiation of GABA-induced inward current, with EC50 values ranging from 8 nM (α5β2γ2) to 128 nM (α3β2γ2). In vitro electrophysiological studies confirmed its ability to reduce excitability of human dorsal root ganglion (DRG) neurons by GABA. LI-633 potentiated muscimol-induced GABAergic currents in rat DRG neurons in a dose-dependent manner, with an EC
conclusionsThese findings highlight the potential of targeting peripheral GABRAs for pain management in disorders associated with visceral hypersensitivity.
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