ArticleNature communications2015
Analgesia and unwanted benzodiazepine effects in point-mutated mice expressing only one benzodiazepine-sensitive GABAA receptor subtype.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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.
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Who cites it
47 citing papers in PubMed.
- The α2-Subunit Preferring GABA Positive Allosteric Modulator, N-Desmethyl-Clobazam in Peripheral Neuropathic Pain Patients: Results of a Phase IIa Randomised Placebo-Controlled Ascending Dose Study.European journal of pain (London, England) · 2026Trial
- Safety, Tolerability, and Pharmacokinetics of Multiple Repeated Oral Doses of the α2/3/5-Subtype Selective GABAClinical pharmacology in drug development · 2021Trial
- Analgesic potential of PF-06372865, an α2/α3/α5 subtype-selective GABABritish journal of anaesthesia · 2019Trial
- Distinct Modulation of High- and Low-Frequency Activity by Midazolam and Neurosteroids in Neocortical Slices.International journal of molecular sciences · 2026Article
- Determining the molecular and physiological actions of subtype-selective nanobodies of GABAScience advances · 2026Article
- The Modulatory Effects of Anesthetics and Analgesics on Neurophysiological Monitoring and Underlying Mechanisms.Current neuropharmacology · 2026Review
- Effects of different anesthetics on remifentanil-induced postinfusion hyperalgesia in patients undergoing percutaneous endoscopic interlaminar discectomy: a randomized controlled trial.Frontiers in medicine · 2025Article
- N-Demethylsinomenine Relieves Neuropathic Pain in Male Mice Mainly via Regulating α2-Subtype GABACNS neuroscience & therapeutics · 2025Article
- Antinociceptive Effects ofThe Journal of pharmacology and experimental therapeutics · 2024Article
- γ1 GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Initial validation of the expectancies for Benzodiazepine Analgesia Scale.Experimental and clinical psychopharmacology · 2024Article
- Preclinical evaluation of ZL006-05, a new antistroke drug with fast-onset antidepressant and anxiolytic effects.Stroke and vascular neurology · 2023Article
- nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story.Neuroscience bulletin · 2023Review
- Shank2 identifies a subset of glycinergic neurons involved in altered nociception in an autism model.Molecular autism · 2023Article
- Potential novel therapeutic strategies for neuropathic pain.Frontiers in molecular neuroscience · 2023Review
- Circuits and components of delta wave regulation.Brain research bulletin · 2022Review
- GABAkines - Advances in the discovery, development, and commercialization of positive allosteric modulators of GABAPharmacology & therapeutics · 2022Review
- Long-term diazepam treatment enhances microglial spine engulfment and impairs cognitive performance via the mitochondrial 18 kDa translocator protein (TSPO).Nature neuroscience · 2022Article
- Modulation of GABAFrontiers in molecular neuroscience · 2022Article
- GABAFrontiers in psychiatry · 2022Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Agonists at the benzodiazepine-binding site of GABAA receptors (BDZs) enhance synaptic inhibition through four subtypes (α1, α2, α3 and α5) of GABAA receptors (GABAAR). When applied to the spinal cord, they alleviate pathological pain; however, insufficient efficacy after systemic administration and undesired effects preclude their use in routine pain therapy. Previous work suggested that subtype-selective drugs might allow separating desired antihyperalgesia from unwanted effects, but the lack of selective agents has hitherto prevented systematic analyses. Here we use four lines of triple GABAAR point-mutated mice, which express only one benzodiazepine-sensitive GABAAR subtype at a time, to show that targeting only α2GABAARs achieves strong antihyperalgesia and reduced side effects (that is, no sedation, motor impairment and tolerance development). Additional pharmacokinetic and pharmacodynamic analyses in these mice explain why clinically relevant antihyperalgesia cannot be achieved with nonselective BDZs. These findings should foster the development of innovative subtype-selective BDZs for novel indications such as chronic pain.
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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.