ArticleMolecular pharmaceutics2016
Development of GABAA Receptor Subtype-Selective Imidazobenzodiazepines as Novel Asthma Treatments.
Article in Molecular pharmaceutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed.
- Lung-Targeted Delivery of Nebulized α‑Asaronol Attenuates Airway Inflammation and Hyperresponsiveness in Murine Asthma Models.ACS pharmacology & translational science · 2026Article
- Metabolomics in Animal Models of Bronchial Asthma and Its Translational Importance for Clinics.International journal of molecular sciences · 2023Review
- Design, Synthesis, and Biological Evaluation of Novel Spiro Imidazobenzodiazepines to Identify Improved Inhaled Bronchodilators.Journal of medicinal chemistry · 2023Article
- Anxiolytics for Bronchodilation: Refinements to GABAAmerican journal of respiratory cell and molecular biology · 2022Article
- Imidazobenzodiazepine PI320 Relaxes Mouse Peripheral Airways by Inhibiting Calcium Mobilization.American journal of respiratory cell and molecular biology · 2022Article
- Comparative pharmacodynamic and pharmacokinetic study of MIDD0301 and its (S) enantiomer.Drug development research · 2022Article
- Development of Inhaled GABAACS pharmacology & translational science · 2022Article
- Identification and Quantification of MIDD0301 Metabolites.Current drug metabolism · 2021Article
- Nebulized MIDD0301 Reduces Airway Hyperresponsiveness in Moderate and Severe Murine Asthma Models.ACS pharmacology & translational science · 2020Article
- A Structure-Activity Relationship Comparison of Imidazodiazepines Binding at Kappa, Mu, and Delta Opioid Receptors and the GABAMolecules (Basel, Switzerland) · 2020Article
- The Effects of pH on the Structure and Bioavailability of Imidazobenzodiazepine-3-Carboxylate MIDD0301.Molecular pharmaceutics · 2020Article
- Novel Expression of GABAA Receptors on Resistance Arteries That Modulate Myogenic Tone.Journal of vascular research · 2020Article
- Pharmacometabolomics of Bronchodilator Response in Asthma and the Role of Age-Metabolite Interactions.Metabolites · 2019Article
- MIDD0301 - A first-in-class anti-inflammatory asthma drug targets GABABasic & clinical pharmacology & toxicology · 2019Article
- Trigeminal neuropathic pain development and maintenance in rats are suppressed by a positive modulator of α6 GABAEuropean journal of pain (London, England) · 2019Article
- A Novel Orally Available Asthma Drug Candidate That Reduces Smooth Muscle Constriction and Inflammation by Targeting GABAMolecular pharmaceutics · 2018Article
- Design and Synthesis of Novel Deuterated Ligands Functionally Selective for the γ-Aminobutyric Acid Type A Receptor (GABAJournal of medicinal chemistry · 2018Article
- Towards functional selectivity for α6β3γ2 GABABritish journal of pharmacology · 2018Article
- Alleviation of Multiple Asthmatic Pathologic Features with Orally Available and Subtype Selective GABAMolecular pharmaceutics · 2017Article
- Optimization of substituted imidazobenzodiazepines as novel asthma treatments.European journal of medicinal chemistry · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors.
Funding
Abstract
Recent studies have demonstrated that subtype-selective GABAA receptor modulators are able to relax precontracted human airway smooth muscle ex vivo and reduce airway hyper-responsiveness in mice upon aerosol administration. Our goal in this study was to investigate systemic administration of subtype-selective GABAA receptor modulators to alleviate bronchoconstriction in a mouse model of asthma. Expression of GABAA receptor subunits was identified in mouse lungs, and the effects of α4-subunit-selective GABAAR modulators, XHE-III-74EE and its metabolite XHE-III-74A, were investigated in a murine model of asthma (ovalbumin sensitized and challenged BALB/c mice). We observed that chronic treatment with XHE-III-74EE significantly reduced airway hyper-responsiveness. In addition, acute treatment with XHE-III-74A but not XHE-III-74EE decreased airway eosinophilia. Immune suppressive activity was also shown in activated human T-cells with a reduction in IL-2 expression and intracellular calcium concentrations [Ca(2+)]i in the presence of GABA or XHE-III-74A, whereas XHE-III-74EE showed only partial reduction of [Ca(2+)]i and no inhibition of IL-2 secretion. However, both compounds significantly relaxed precontracted tracheal rings ex vivo. Overall, we conclude that the systemic delivery of a α4-subunit-selective GABAAR modulator shows good potential for a novel asthma therapy; however, the pharmacokinetic properties of this class of drug candidates have to be improved to enable better beneficial systemic pharmacodynamic effects.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.