ArticleThe Journal of biological chemistry2010
In silico docking and electrophysiological characterization of lacosamide binding sites on collapsin response mediator protein-2 identifies a pocket important in modulating sodium channel slow inactivation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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Who cites it
40 citing papers in PubMed, 76 citations in OpenAlex.
- Unlocking New Therapeutic Options for Vincristine-Induced Neuropathic Pain: The Impact of Preclinical Research.Life (Basel, Switzerland) · 2024Review
- Dihydropyrimidinase-like 2 can serve as a novel therapeutic target and prognostic biomarker in acute myeloid leukemia.Cancer medicine · 2023Article
- In Silico Identification of Promising New Pyrazole Derivative-Based Small Molecules for Modulating CRMP2, C-RAF, CYP17, VEGFR, C-KIT, and HDAC-Application towards Cancer Therapeutics.Current issues in molecular biology · 2022Article
- The protective effect of chemical and natural compounds against vincristine-induced peripheral neuropathy (VIPN).Naunyn-Schmiedeberg's archives of pharmacology · 2022Review
- Novel Compounds Targeting Neuropilin Receptor 1 with Potential To Interfere with SARS-CoV-2 Virus Entry.ACS chemical neuroscience · 2021Article
- Anticonvulsant vs. Proconvulsant Effect ofFrontiers in systems neuroscience · 2021Article
- Lacosamide intake during pregnancy increases the incidence of foetal malformations and symptoms associated with schizophrenia in the offspring of mice.Scientific reports · 2020Article
- Dysregulation of CRMP2 Post-Translational Modifications Drive Its Pathological Functions.Molecular neurobiology · 2019Review
- Phosphorylated CRMP2 Regulates Spinal Nociceptive Neurotransmission.Molecular neurobiology · 2019Article
- Mapping protein interactions of sodium channel NaThe EMBO journal · 2018Article
- Article
- mTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors.Molecular psychiatry · 2017Article
- Article
- Role of Sodium Channels in Epilepsy.Cold Spring Harbor perspectives in medicine · 2016Review
- (S)-Lacosamide Binding to Collapsin Response Mediator Protein 2 (CRMP2) Regulates CaV2.2 Activity by Subverting Its Phosphorylation by Cdk5.Molecular neurobiology · 2016Article
- Safety of lacosamide in children with refractory partial epilepsy.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2015Article
- CRMPs: critical molecules for neurite morphogenesis and neuropsychiatric diseases.Molecular psychiatry · 2015Review
- 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
- Specific binding of lacosamide to collapsin response mediator protein 2 (CRMP2) and direct impairment of its canonical function: implications for the therapeutic potential of lacosamide.Molecular neurobiology · 2015Review
- 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
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The anti-epileptic drug (R)-lacosamide ((2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide (LCM)) modulates voltage-gated sodium channels (VGSCs) by preferentially interacting with slow inactivated sodium channels, but the observation that LCM binds to collapsin response mediator protein 2 (CRMP-2) suggests additional mechanisms of action for LCM. We postulated that CRMP-2 levels affects the actions of LCM on VGSCs. CRMP-2 labeling by LCM analogs was competitively displaced by excess LCM in rat brain lysates. Manipulation of CRMP-2 levels in the neuronal model system CAD cells affected slow inactivation of VGSCs without any effects on other voltage-dependent properties. In silico docking was performed to identify putative binding sites in CRMP-2 that may modulate the effects of LCM on VGSCs. These studies identified five cavities in CRMP-2 that can accommodate LCM. CRMP-2 alanine mutants of key residues within these cavities were functionally similar to wild-type CRMP-2 as assessed by similar levels of enhancement in dendritic complexity of cortical neurons. Next, we examined the effects of expression of wild-type and mutant CRMP-2 constructs on voltage-sensitive properties of VGSCs in CAD cells: 1) steady-state voltage-dependent activation and fast-inactivation properties were not affected by LCM, 2) CRMP-2 single alanine mutants reduced the LCM-mediated effects on the ability of endogenous Na(+) channels to transition to a slow inactivated state, and 3) a quintuplicate CRMP-2 alanine mutant further decreased this slow inactivated fraction. Collectively, these results identify key CRMP-2 residues that can coordinate LCM binding thus making it more effective on its primary clinical target.
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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.