ArticleProceedings of the National Academy of Sciences of the United States of America2014
Local anesthetic and antiepileptic drug access and binding to a bacterial voltage-gated sodium channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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
57 citing papers in PubMed, 103 citations in OpenAlex.
- General anesthetic modulation of a pentameric ligand-gated ion channel explored with simulations.Biophysical journal · 2026Article
- A promising novel local anesthetic for effective anesthesia in oral inflammatory conditions through reducing mitochondria-related apoptosis.Acta pharmaceutica Sinica. B · 2025Article
- Drugs exhibit diverse binding modes and access routes in the Nav1.5 cardiac sodium channel pore.The Journal of general physiology · 2025Article
- Reactivity of Olanzapine and Tricyclic Antidepressants on the Protective Effects of Trolox on Lipid Peroxidation Evaluated Using Fluorescence Anisotropy, Electron Paramagnetic Resonance Spectrometry, and Thermal Analysis.ACS chemical neuroscience · 2025Article
- Inhibition of NMDA receptors and other ion channel types by membrane-associated drugs.Frontiers in pharmacology · 2025Review
- The chemistry of electrical signaling in sodium channels from bacteria and beyond.Cell chemical biology · 2024Review
- In Silico Screening Identification of Fatty Acids and Fatty Acid Derivatives with Antiseizure Activity: In Vitro and In Vivo Validation.Pharmaceutics · 2024Article
- Unplugging lateral fenestrations of NALCN reveals a hidden drug binding site within the pore region.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Calcium-gated potassium channel blockade via membrane-facing fenestrations.Nature chemical biology · 2024Article
- Cannabidiol inhibits NaNature communications · 2023Article
- Effects of Local Anesthetics on Liposomal Membranes Determined by Their Inhibitory Activity of Lipid Peroxidation.Molecular pharmaceutics · 2023Article
- Article
- Inhibition of NMDA receptors through a membrane-to-channel path.Nature communications · 2022Article
- Characterizing fenestration size in sodium channel subtypes and their accessibility to inhibitors.Biophysical journal · 2022Article
- Article
- Structural Advances in Voltage-Gated Sodium Channels.Frontiers in pharmacology · 2022Review
- Sodium Channels and Local Anesthetics-Old Friends With New Perspectives.Frontiers in pharmacology · 2022Review
- Article
- Molecular determinants of pro-arrhythmia proclivity of d- and l-sotalol via a multi-scale modeling pipeline.Journal of molecular and cellular cardiology · 2021Article
- Local anesthetics impair the growth and self-renewal of glioblastoma stem cells by inhibiting ZDHHC15-mediated GP130 palmitoylation.Stem cell research & therapy · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Voltage-gated sodium (Nav) channels are important targets in the treatment of a range of pathologies. Bacterial channels, for which crystal structures have been solved, exhibit modulation by local anesthetic and anti-epileptic agents, allowing molecular-level investigations into sodium channel-drug interactions. These structures reveal no basis for the "hinged lid"-based fast inactivation, seen in eukaryotic Nav channels. Thus, they enable examination of potential mechanisms of use- or state-dependent drug action based on activation gating, or slower pore-based inactivation processes. Multimicrosecond simulations of NavAb reveal high-affinity binding of benzocaine to F203 that is a surrogate for FS6, conserved in helix S6 of Domain IV of mammalian sodium channels, as well as low-affinity sites suggested to stabilize different states of the channel. Phenytoin exhibits a different binding distribution owing to preferential interactions at the membrane and water-protein interfaces. Two drug-access pathways into the pore are observed: via lateral fenestrations connecting to the membrane lipid phase, as well as via an aqueous pathway through the intracellular activation gate, despite being closed. These observations provide insight into drug modulation that will guide further developments of Nav inhibitors.
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.