ArticleMolecular pharmacology2014
Block of human cardiac sodium channels by lacosamide: evidence for slow drug binding along the activation pathway.
Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Advances in Sodium Channel Modulation in Epilepsy Therapy: Focus on Eslicarbazepine, Lacosamide and Cenobamate.Biomedicines · 2026Review
- Blocking the voltage-gated sodium channel hNaFEBS open bio · 2025Article
- Severe Bradycardia and Shock With Delayed Onset Due to Lacosamide Overdose: A Case Report.Cureus · 2025Article
- State-Dependent Blockade of Dorsal Root Ganglion Voltage-Gated NaInternational journal of molecular sciences · 2024Article
- Block of Voltage-Gated Sodium Channels by Aripiprazole in a State-Dependent Manner.International journal of molecular sciences · 2022Article
- Effective Modulation by Lacosamide on Cumulative Inhibition ofInternational journal of molecular sciences · 2022Article
- Evidence for Inhibitory Perturbations on the Amplitude, Gating, and Hysteresis of A-Type Potassium Current, Produced by Lacosamide, a Functionalized Amino Acid with Anticonvulsant Properties.International journal of molecular sciences · 2022Article
- Article
- Modelling of an autonomous Nav1.5 channel system as a part of in silico pharmacology study.Journal of molecular modeling · 2021Article
- Lacosamide Inhibition of NaFrontiers in pharmacology · 2021Article
- Block of Voltage-Gated Sodium Channels by Atomoxetine in a State- and Use-dependent Manner.Frontiers in pharmacology · 2021Article
- Lidocaine Binding Enhances Inhibition of Nav1.7 Channels by the Sulfonamide PF-05089771.Molecular pharmacology · 2020Article
- Kir2 inward rectification-controlled precise and dynamic balances between Kir2 and HCN currents initiate pacemaking activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- State-dependent block of voltage-gated sodium channels by the casein-kinase 1 inhibitor IC261.Investigational new drugs · 2017Article
- Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants.The Journal of general physiology · 2017Article
- Lacosamide Inhibition of Nav1.7 Voltage-Gated Sodium Channels: Slow Binding to Fast-Inactivated States.Molecular pharmacology · 2017Article
- Inhibitory effects of hesperetin on Nav1.5 channels stably expressed in HEK 293 cells and on the voltage-gated cardiac sodium current in human atrial myocytes.Acta pharmacologica Sinica · 2016Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Lacosamide is an anticonvulsant hypothesized to enhance slow inactivation of neuronal Na(+) channels for its therapeutic action. Cardiac Na(+) channels display less and incomplete slow inactivation, but their sensitivity toward lacosamide remains unknown. We therefore investigated the action of lacosamide in human cardiac Nav1.5 and Nav1.5-CW inactivation-deficient Na(+) channels. Lacosamide showed little effect on hNav1.5 Na(+) currents at 300 µM when cells were held at -140 mV. With 30-second conditioning pulses from -90 to -50 mV; however, hNav1.5 Na(+) channels became sensitive to lacosamide with IC50 (50% inhibitory concentration) around 70-80 µM. Higher IC50 values were found at -110 and -30 mV. The development of lacosamide block at -70 mV was slow in wild-type Na(+) channels (τ; 8.04 ± 0.39 seconds, n = 8). This time constant was significantly accelerated in hNav1.5-CW inactivation-deficient counterparts. The recovery from lacosamide block at -70 mV for 10 seconds was relatively rapid in wild-type Na(+) channels (τ; 639 ± 90 milliseconds, n = 8). This recovery was accelerated further in hNav1.5-CW counterparts. Unexpectedly, lacosamide elicited a time-dependent block of persistent hNav1.5-CW Na(+) currents with an IC50 of 242 ± 19 µM (n = 5). Furthermore, both hNav1.5-CW/F1760K mutant and batrachotoxin-activated hNav1.5 Na(+) channels became completely lacosamide resistant, indicating that the lacosamide receptor overlaps receptors for local anesthetics and batrachotoxin. Our results together suggest that lacosamide targets the intermediate preopen and open states of hNav1.5 Na(+) channels. Lacosamide may thus track closely the conformational changes at the hNav1.5-F1760 region along the activation pathway.
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