ArticlePloS one2014
Clobazam and its active metabolite N-desmethylclobazam display significantly greater affinities for α₂- versus α₁-GABA(A)-receptor complexes.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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.
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Who cites it
27 citing papers in PubMed, 62 citations in OpenAlex.
- Efficacy and safety of adjunctive padsevonil in adults with drug-resistant focal epilepsy: Results from two double-blind, randomized, placebo-controlled trials.Epilepsia open · 2022Trial
- Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study.Neurology · 2016Trial
- Clobazam in pediatric drug-resistant epilepsy: from pharmacology to clinical practice.European journal of clinical pharmacology · 2026Review
- Review
- Which are the options and dosages for clobazam shortages on epilepsy treatment? Review of literature and survey of specialists.Arquivos de neuro-psiquiatria · 2025Review
- Efficacy and Safety of Clobazam Adjunctive Therapy in Pediatric Patients with Drug-Resistant Epilepsy.Drug design, development and therapy · 2025Article
- Use of Passive and Grab Sampling and High-Resolution Mass Spectrometry for Non-Targeted Analysis of Emerging Contaminants and Their Semi-Quantification in Water.Molecules (Basel, Switzerland) · 2022Article
- Use of Interval Therapy with Benzodiazepines to Prevent Seizure Recurrence in Stressful Situations.Brain sciences · 2022Article
- Macroglossia Associated With Clobazam Administration: A Case Report and Literature Review.Frontiers in neurology · 2022Article
- Treatment and care of women with epilepsy before, during, and after pregnancy: a practical guide.Therapeutic advances in neurological disorders · 2022Review
- Efficacy and Tolerability of Clobazam in Adults With Drug-Refractory Epilepsy.Neurology. Clinical practice · 2021Article
- Antiepileptic Drugs-Induced Enuresis in Children: An Overview.The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians · 2021Article
- Molecular Targets of Cannabidiol in Experimental Models of Neurological Disease.Molecules (Basel, Switzerland) · 2020Review
- Rare but life-threatening aspiration pneumonia related to initiation of clobazam therapy.Epilepsy & behavior reports · 2020Article
- Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions.Epilepsia · 2019Article
- A Phase 1, Open-Label, Pharmacokinetic Trial to Investigate Possible Drug-Drug Interactions Between Clobazam, Stiripentol, or Valproate and Cannabidiol in Healthy Subjects.Clinical pharmacology in drug development · 2019Article
- Potentiating αThe Journal of physiology · 2019Article
- Effects of antiepileptic drugs in a new TSC/mTOR-dependent epilepsy mouse model.Annals of clinical and translational neurology · 2019Article
- A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam.Journal of clinical pharmacology · 2019Review
- PharmGKB summary: clobazam pathway, pharmacokinetics.Pharmacogenetics and genomics · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clobazam (CLB), a 1,5-benzodiazepine (BZD), was FDA-approved in October 2011 for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years and older. BZDs exert various CNS effects through allosteric modulation of GABAA receptors. The structurally distinct, 1,4-BZD clonazepam (CLN) is also approved to treat LGS. The precise mechanisms of action and clinical efficacy of both are unknown. Data show that the GABAA α₁-subunit-selective compound zolpidem [ZOL] exhibits hypnotic/sedative effects. Conversely, data from knock-in mice carrying BZD binding site mutations suggest that the α₂ subunit mediates anticonvulsant effects, without sedative actions. Hence, the specific pattern of interactions across the GABAA receptor complexes of BZDs might be reflected in their clinical efficacies and adverse effect profiles. In this study, GABAA-receptor binding affinities of CLB, N-desmethylclobazam (N-CLB, the major metabolite of CLB), CLN, and ZOL were characterized with native receptors from rat-brain homogenates and on cloned receptors from HEK293 cells transfected with combinations of α (α₁, α₂, α₃, or α₅), β₂, and γ₂ subtypes. Our results demonstrate that CLB and N-CLB have significantly greater binding affinities for α₂- vs. α₁-receptor complexes, a difference not observed for CLN, for which no distinction between α₂ and α₁ receptors was observed. Our experiments with ZOL confirmed the high preference for α₁ receptors. These results provide potential clues to a new understanding of the pharmacologic modes of action of CLB and N-CLB.
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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.