ArticleThe Journal of general physiology2017
Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants.
Article in The Journal of general physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Centipede Venom Peptides Acting on Ion Channels.Toxins · 2020Pooled it
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- Chasing the Wrong Door for 30 Years: Is Suzetrigine the Key to Selective Pain Relief?Medicina (Kaunas, Lithuania) · 2026Review
- Efficacy of Ultrasound-Guided Intercostal Nerve Block With Liposomal Bupivacaine for Treating Postherpetic Neuralgia in Adult Patients.The Kaohsiung journal of medical sciences · 2026Article
- Advances in Sodium Channel Modulation in Epilepsy Therapy: Focus on Eslicarbazepine, Lacosamide and Cenobamate.Biomedicines · 2026Review
- Multimodal analgesia with continuous nerve blocks versus intravenous patient-controlled analgesia for pancreatectomy: a retrospective cohort study.Perioperative medicine (London, England) · 2026Article
- From ion channel biology to clinical practice: suzetrigine as a precision analgesic.Frontiers in medicine · 2026Review
- A venom fraction from the Philippine tarantula (The journal of venomous animals and toxins including tropical diseases · 2026Article
- Dermal Concentration Versus Systemic Bioavailability of Topical Lidocaine and Tetracaine: An Exploratory Pharmacokinetic Pilot Study in Göttingen Minipigs.Pharmaceutics · 2025Article
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- Drugs exhibit diverse binding modes and access routes in the Nav1.5 cardiac sodium channel pore.The Journal of general physiology · 2025Article
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- 3D-aligned tetrameric ion channels with universal residue labels for comparative structural analysis.Biophysical journal · 2025Article
- Antiseizure Medications: Advancements, Challenges, and Prospects in Drug Development.Current neuropharmacology · 2025Review
- Chest pain management in acute coronary syndrome and chronic stable angina with diluted xylocaine injections.Bioinformation · 2025Article
- Neuromodulators in Acute and Chronic Cough in Children: An Update from the Literature.International journal of molecular sciences · 2024Review
- Efficacy and safety of ketamine wound infiltration for postoperative pain management: a systematic review, meta-analysis, and trial sequential analysis.Annals of medicine and surgery (2012) · 2024Review
- Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia.International journal of molecular sciences · 2024Review
- The Stable Gastric Pentadecapeptide BPC 157 Pleiotropic Beneficial Activity and Its Possible Relations with Neurotransmitter Activity.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Suspected local anesthetic resistance after intrathecal, perineural, intraarticular and subcutaneous injections: a case report.AME case reports · 2024Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Local anesthetics, antiarrhythmics, and anticonvulsants include both charged and electroneutral compounds that block voltage-gated sodium channels. Prior studies have revealed a common drug-binding region within the pore, but details about the binding sites and mechanism of block remain unclear. Here, we use the x-ray structure of a prokaryotic sodium channel, NavMs, to model a eukaryotic channel and dock representative ligands. These include lidocaine, QX-314, cocaine, quinidine, lamotrigine, carbamazepine (CMZ), phenytoin, lacosamide, sipatrigine, and bisphenol A. Preliminary calculations demonstrated that a sodium ion near the selectivity filter attracts electroneutral CMZ but repels cationic lidocaine. Therefore, we further docked electroneutral and cationic drugs with and without a sodium ion, respectively. In our models, all the drugs interact with a phenylalanine in helix IVS6. Electroneutral drugs trap a sodium ion in the proximity of the selectivity filter, and this same site attracts the charged group of cationic ligands. At this position, even small drugs can block the permeation pathway by an electrostatic or steric mechanism. Our study proposes a common pharmacophore for these diverse drugs. It includes a cationic moiety and an aromatic moiety, which are usually linked by four bonds.
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