ArticleACS chemical neuroscience2011
Development and characterization of novel derivatives of the antiepileptic drug lacosamide that exhibit far greater enhancement in slow inactivation of voltage-gated sodium channels.
Article in ACS chemical neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Chiral (Stereoselective) Drugs, Asymmetric Synthesis, and Racemic Resolution Methods.Chirality · 2026Review
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- Selective targeting of NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces pain in rodents.Science translational medicine · 2021Article
- Lacosamide Inhibition of NaFrontiers in pharmacology · 2021Article
- Article
- Article
- Lacosamide Inhibition of Nav1.7 Voltage-Gated Sodium Channels: Slow Binding to Fast-Inactivated States.Molecular pharmacology · 2017Article
- Hierarchical CRMP2 posttranslational modifications control NaV1.7 function.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Direct and cost-efficient hyperpolarization of long-lived nuclear spin states on universal (15)N2-diazirine molecular tags.Science advances · 2016Article
- Chimeric derivatives of functionalized amino acids and α-aminoamides: compounds with anticonvulsant activity in seizure models and inhibitory actions on central, peripheral, and cardiac isoforms of voltage-gated sodium channels.Bioorganic & medicinal chemistry · 2015Article
- Chimeric agents derived from the functionalized amino acid, lacosamide, and the α-aminoamide, safinamide: evaluation of their inhibitory actions on voltage-gated sodium channels, and antiseizure and antinociception activities and comparison with lacosamide and safinamide.ACS chemical neuroscience · 2015Article
- Current understanding of the mechanism of action of the antiepileptic drug lacosamide.Epilepsy research · 2015Review
- Substituted N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamides: potent anticonvulsants that affect frequency (use) dependence and slow inactivation of sodium channels.Journal of medicinal chemistry · 2014Article
- Development of a new photochromic ion channel blocker via azologization of fomocaine.ACS chemical neuroscience · 2014Article
- CRMP2 protein SUMOylation modulates NaV1.7 channel trafficking.The Journal of biological chemistry · 2013Article
- (Biphenyl-4-yl)methylammonium chlorides: potent anticonvulsants that modulate Na+ currents.Journal of medicinal chemistry · 2013Article
- Discovery of lacosamide affinity bait agents that exhibit potent voltage-gated sodium channel blocking properties.ACS chemical neuroscience · 2013Article
- Identification of the benzyloxyphenyl pharmacophore: a structural unit that promotes sodium channel slow inactivation.ACS chemical neuroscience · 2012Article
- QUANTITATIVE RT-PCR ANALYSES OF FIVE EVOLUTIONARY CONSERVED GENES IN ALLIGATOR BRAINS DURING DEVELOPMENT.Translational neuroscience · 2011Article
- Identification of a lacosamide binding protein using an affinity bait and chemical reporter strategy: 14-3-3 ζ.Journal of the American Chemical Society · 2011Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The novel antiepileptic drug, (R)-N-benzyl 2-acetamido-3-methoxypropionamide ((R)-lacosamide, Vimpat(®) ((R)-1)), was recently approved in the US and Europe for adjuvant treatment of partial-onset seizures in adults. (R)-1 preferentially enhances slow inactivation of voltage-gated Na(+) currents, a pharmacological process relevant in the hyperexcitable neuron. We have advanced a strategy to identify lacosamide binding partners by attaching affinity bait (AB) and chemical reporter (CR) groups to (R)-1 to aid receptor detection and isolation. We showed that select lacosamide AB and AB&CR derivatives exhibited excellent activities similar to (R)-1 in the maximal electroshock seizure model in rodents. Here, we examined the effect of these lacosamide AB and AB&CR derivatives and compared them with (R)-1 on Na(+) channel function in CNS catecholaminergic (CAD) cells. Using whole-cell patch clamp electrophysiology, we demonstrated that the test compounds do not affect the Na(+) channel fast inactivation process, that they were far better modulators of slow inactivation than (R)-1, and that modulation of the slow inactivation process was stereospecific. The lacosamide AB agents that contained either an electrophilic isothiocyanate ((R)-5) or a photolabile azide ((R)-8) unit upon AB activation gave modest levels of permanent Na(+) channel slow inactivation, providing initial evidence that these compounds may have covalently reacted with their cognate receptor(s). Our findings support the further use of these agents to delineate the (R)-1-mediated Na(+) channel slow inactivation process.
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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.