The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels.

The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Abstract Text:

Adam C Errington,Thomas ,Cara Heers,George Lees,Adam C Errington,Thomas ,Cara Heers,George Lees,Adam C Errington,Thomas ,Cara Heers,George Lees,Adam C Errington,Thomas ,Cara Heers,George Lees,

We hypothesized that lacosamide modulates voltage-gated sodium channels (VGSCs) at clinical concentrations (32-100 muM). Lacosamide reduced spiking evoked in cultured rat cortical neurons by 30-s depolarizing ramps but not by 1-s ramps. Carbamazepine and phenytoin reduced spike-firing induced by both ramps. Lacosamide inhibited sustained repetitive firing during a 10-s burst but not within the first second. Tetrodotoxin-sensitive VGSC currents in N1E-115 cells were reduced by 100 muM lacosamide, carbamazepine, lamotrigine, and phenytoin from V(h) of -60 mV. Hyperpolarization (500 ms) to -100 mV removed the block by carbamazepine, lamotrigine, and phenytoin but not by lacosamide. The voltage-dependence of activation was not changed by lacosamide. The inactive S-stereoisomer did not inhibit VGSCs. Steady-state fast inactivation curves were shifted in the hyperpolarizing direction by carbamazepine, lamotrigine, and phenytoin but not at all by lacosamide. Lacosamide did not retard recovery from fast inactivation in contrast to carbamazepine. Carbamazepine, lamotrigine, and phenytoin but not lacosamide all produced frequency-dependent facilitation of block of a 3-s, 10-Hz pulse train. Lacosamide shifted the slow inactivation voltage curve in the hyperpolarizing direction and significantly promoted the entry of channels into the slow inactivated state (carbamazepine weakly impaired entry into the slow inactivated state) without altering the rate of recovery. Lacosamide is the only analgesic/anticonvulsant drug that reduces VGSC availability by selective enhancement of slow inactivation but without apparent interaction with fast inactivation gating. The implications of this unique profile are being explored in phase III clinical trials for epilepsy and neuropathic pain.

The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Publishing Authors By Initials

AC Errington,T ,C Heers,G Lees,AC Errington,T ,C Heers,G Lees,AC Errington,T ,C Heers,G Lees,AC Errington,T ,C Heers,G Lees,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Molecular pharmacology

VOLUME: 73

Page Numbers: 157-69

Journal Abbreviation: Mol. Pharmacol.

ISSN: 1521-0111

DAY: 16

MONTH: 10

YEAR: 2007

The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 35623

The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels.

AFFILIATION: Department of Pharmacology and Toxicology, Otago School of Medical Sciences, University of Otago, PO Box 913, Dunedin, New Zealand. george.lees@stonebow.otago.ac.nz.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Mol Pharmacol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels Related Publications

• A new method of applying the screen test for inter-ocular muscle balance.
• A statistical and clinical review of 107 cases of ectopic gestation.
• Acute stroke: we have the treatments and we have the evidence--we need to use them.
• Advances in emerging therapies 2007.
• Balancing conformational and oxidative kinetic traps during the folding of bovine pancreatic trypsin inhibitor (BPTI) with glutathione and glutathione disulfide.
• DIAGNOSIS OF DIPLOPIA.
• Effects of the Occupational Safety and Health Administration's control of hazardous energy (lockout/tagout) standard on rates of machinery-related fatal occupational injury.
• FoxO3a preferentially induces p27(Kip1) expression while impairing muscle precursor cell-cycle progression.
• Immunologic studies of subjects with asthma exposed to formaldehyde and urea-formaldehyde foam insulation (UFFI) off products.
• Issues pertaining to the critiques of the SAINT-I Trial.
• Life and death decisions by the E2F transcription factors.
• Modern concepts of instinctive behaviour.
• Parkinson's disease with Onuf's nucleus involvement mimicking multiple system atrophy.
• Prediction and perinatal outcomes of fetal growth restriction.
• Prevention of atherosclerosis progression in asymptomatic healthy elderly.
• Punding in Parkinson's disease.
• Quantitative secretin MRCP (MRCPQ): results in 215 patients with known or suspected pancreatic pathology.
• RECTAL NARCOSIS IN OPHTHALMIC SURGERY.
• Repeatability of high-frequency distortion-product otoacoustic emissions in normal-hearing adults.
• SYNTHESIS OF UNSATURATED FATTY ACIDS IN THE SLIME MOLD PHYSARUM POLYCEPHALUM AND THE ZOOFLAGELLATES LEISHMANIA TARENTOLAE, TRYPANOSOMA LEWISI, AND CRITHIDIA SP.: A COMPARATIVE STUDY.
• Selective requirements for E2f3 in the development and tumorigenicity of Rb-deficient chimeric tissues.
• THE USE OF UNIT CELLS IN THE LISTER MORTON OPHTHALMOSCOPE.
• The effects of intravenous hyperalimentation on plasma proteins in severe hypercholesterolemia [proceedings].
• The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels.
• The teaching of venereology.
• Time spent at home poststroke: "home-time" a meaningful and robust outcome measure for stroke trials.
• Tuberculosis among medical and academic students.
• Unresolved issues relating to the shaking palsy on the celebration of James Parkinson's 250th birthday.
• WITHDRAWN: Institutional versus at-home long term care for functionally dependent older people.
• catena-Poly[[bis(nitrato-kappa(2)O,O')copper(II)]-mu-propane-1,3-diylbis(diphenylphosphine oxide)-kappa(2)O:O'].