ArticleACS chemical neuroscience2011
Merging Structural Motifs of Functionalized Amino Acids and α-Aminoamides Results in Novel Anticonvulsant Compounds with Significant Effects on Slow and Fast Inactivation of Voltage-gated Sodium Channels and in the Treatment of Neuropathic Pain.
Article in ACS chemical neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05603702 (STTEPP), which is not on this map. Cited by 24 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.
STTEPP: Safety, Tolerability and Dose Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis
Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Safety, Tolerability, and Dose-Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis: Protocol for a Phase 1 Clinical Trial to Determine Safety and Identify Side Effects.JMIR research protocols · 2024Article
- Effective Modulation by Lacosamide on Cumulative Inhibition ofInternational journal of molecular sciences · 2022Article
- Synthesis and Evaluation of Novel α-Aminoamides Containing Benzoheterocyclic Moiety for the Treatment of Pain.Molecules (Basel, Switzerland) · 2021Article
- Pharmacological characterization of crotamine effects on mice hind limb paralysis employing both ex vivo and in vivo assays: Insights into the involvement of voltage-gated ion channels in the crotamine action on skeletal muscles.PLoS neglected tropical diseases · 2018Article
- 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
- Article
- Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain.Molecules (Basel, Switzerland) · 2016Article
- Efficacy of (Pain reports · 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
- 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
- Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain.PloS one · 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
- Suppression of pain-related behavior in two distinct rodent models of peripheral neuropathy by a homopolyarginine-conjugated CRMP2 peptide.Journal of neurochemistry · 2013Article
- Identification of the benzyloxyphenyl pharmacophore: a structural unit that promotes sodium channel slow inactivation.ACS chemical neuroscience · 2012Article
- Inhibition of transmitter release and attenuation of anti-retroviral-associated and tibial nerve injury-related painful peripheral neuropathy by novel synthetic Ca2+ channel peptides.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
We recently reported that merging key structural pharmacophores of the anticonvulsant drugs lacosamide (a functionalized amino acid) with safinamide (an α-aminoamide) resulted in novel compounds with anticonvulsant activities superior to that of either drug alone. Here, we examined the effects of six such chimeric compounds on Na(+)-channel function in central nervous system catecholaminergic (CAD) cells. Using whole-cell patch clamp electrophysiology, we demonstrated that these compounds affected Na(+) channel fast and slow inactivation processes. Detailed electrophysiological characterization of two of these chimeric compounds that contained either an oxymethylene ((R)-7) or a chemical bond ((R)-11) between the two aromatic rings showed comparable effects on slow inactivation, use-dependence of block, development of slow inactivation, and recovery of Na(+) channels from inactivation. Both compounds were equally effective at inducing slow inactivation; (R)-7 shifted the fast inactivation curve in the hyperpolarizing direction greater than (R)-11, suggesting that in the presence of (R)-7, a larger fraction of the channels are in an inactivated state. None of the chimeric compounds affected veratridine- or KCl-induced glutamate release in neonatal cortical neurons. There was modest inhibition of KCl-induced calcium influx in cortical neurons. Finally, a single intraperitoneal administration of (R)-7, but not (R)-11, completely reversed mechanical hypersensitivity in a tibial-nerve injury model of neuropathic pain. The strong effects of (R)-7 on slow and fast inactivation of Na(+) channels may contribute to its efficacy and provide a promising novel therapy for neuropathic pain, in addition to its antiepileptic potential.
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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.