sodium channel blockers

Summary

Summary: A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.

Top Publications

  1. ncbi International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels
    William A Catterall
    Department of Pharmacology, University of Washington, Mailstop 357280, Seattle, WA 98195 7280
    Pharmacol Rev 57:397-409. 2005
  2. ncbi Voltage-gated sodium channels and pain pathways
    John N Wood
    Molecular Nociception Group, Department of Biology, University College, Gower Street, London WC1E 6BT, UK
    J Neurobiol 61:55-71. 2004
  3. ncbi Action potential generation requires a high sodium channel density in the axon initial segment
    Maarten H P Kole
    Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Garran Road, Canberra ACT 0200, Australia
    Nat Neurosci 11:178-86. 2008
  4. ncbi Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders
    Massimo Mantegazza
    Dipartimento di Neurofisiopatologia, Fondazione Istituto Neurologico C Besta, Milano, Italy
    Lancet Neurol 9:413-24. 2010
  5. ncbi Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers
    Alexander M Binshtok
    Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Nature 449:607-10. 2007
  6. pmc The Na channel voltage sensor associated with inactivation is localized to the external charged residues of domain IV, S4
    M F Sheets
    The Nora Eccles Harrison Cardiovascular Research and Training Institute and Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84112, USA
    Biophys J 77:747-57. 1999
  7. pmc The tetrodotoxin binding site is within the outer vestibule of the sodium channel
    Harry A Fozzard
    Department of Medicine, University of Chicago Hospitals, Chicago, IL 60637, USA
    Mar Drugs 8:219-34. 2010
  8. pmc muO-conotoxin MrVIB selectively blocks Nav1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits
    J Ekberg
    Institute for Molecular Bioscience and School of Biomedical Sciences, University of Queensland, QLD 4072, Australia
    Proc Natl Acad Sci U S A 103:17030-5. 2006
  9. pmc Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and -resistant sodium channels in dorsal root ganglion neurons in the rat
    Shuangsong Hong
    Department of Internal Medicine and Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 279:29341-50. 2004
  10. ncbi Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP
    V Monica Bricelj
    Institute for Marine Biosciences, National Research Council, Halifax, Nova Scotia B3H 3Z1, Canada
    Nature 434:763-7. 2005

Detail Information

Publications261 found, 100 shown here

  1. ncbi International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels
    William A Catterall
    Department of Pharmacology, University of Washington, Mailstop 357280, Seattle, WA 98195 7280
    Pharmacol Rev 57:397-409. 2005
    ..This article presents the molecular relationships and physiological roles of these sodium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties...
  2. ncbi Voltage-gated sodium channels and pain pathways
    John N Wood
    Molecular Nociception Group, Department of Biology, University College, Gower Street, London WC1E 6BT, UK
    J Neurobiol 61:55-71. 2004
    Acute, inflammatory, and neuropathic pain can all be attenuated or abolished by local treatment with sodium channel blockers such as lidocaine...
  3. ncbi Action potential generation requires a high sodium channel density in the axon initial segment
    Maarten H P Kole
    Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Garran Road, Canberra ACT 0200, Australia
    Nat Neurosci 11:178-86. 2008
    ..In conclusion, action potential generation requires a high Na(+) channel density at the AIS, which is maintained by tight anchoring to the actin cytoskeleton...
  4. ncbi Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders
    Massimo Mantegazza
    Dipartimento di Neurofisiopatologia, Fondazione Istituto Neurologico C Besta, Milano, Italy
    Lancet Neurol 9:413-24. 2010
    ....
  5. ncbi Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers
    Alexander M Binshtok
    Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Nature 449:607-10. 2007
    ....
  6. pmc The Na channel voltage sensor associated with inactivation is localized to the external charged residues of domain IV, S4
    M F Sheets
    The Nora Eccles Harrison Cardiovascular Research and Training Institute and Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84112, USA
    Biophys J 77:747-57. 1999
    ....
  7. pmc The tetrodotoxin binding site is within the outer vestibule of the sodium channel
    Harry A Fozzard
    Department of Medicine, University of Chicago Hospitals, Chicago, IL 60637, USA
    Mar Drugs 8:219-34. 2010
    ..One site in the channel's domain I P loop determines affinity differences in mammalian isoforms...
  8. pmc muO-conotoxin MrVIB selectively blocks Nav1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits
    J Ekberg
    Institute for Molecular Bioscience and School of Biomedical Sciences, University of Queensland, QLD 4072, Australia
    Proc Natl Acad Sci U S A 103:17030-5. 2006
    ..The actions of MrVIB reveal that VGSC antagonists displaying selectivity toward Na(v)1.8 can alleviate chronic pain behavior with a greater therapeutic index than nonselective antagonists...
  9. pmc Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and -resistant sodium channels in dorsal root ganglion neurons in the rat
    Shuangsong Hong
    Department of Internal Medicine and Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 279:29341-50. 2004
    ..These results suggest that both TTX-S and TTX-R sodium channels play important roles and that differential phosphorylation of sodium channels involving both serine/threonine and tyrosine sites contributes to painful diabetic neuropathy...
  10. ncbi Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP
    V Monica Bricelj
    Institute for Marine Biosciences, National Research Council, Halifax, Nova Scotia B3H 3Z1, Canada
    Nature 434:763-7. 2005
    ..Furthermore, global expansion of PSP to previously unaffected coastal areas might result in long-term changes to communities and ecosystems...
  11. pmc Different flecainide sensitivity of hNav1.4 channels and myotonic mutants explained by state-dependent block
    Jean Francois Desaphy
    Division of Pharmacology, Department of Pharmaco Biology, University of Bari, Bari I 70125, Italy
    J Physiol 554:321-34. 2004
    ..This study offers a pharmacogenetic strategy to better address treatment in individual myotonic patients...
  12. ncbi Reduction of repolarization reserve unmasks the proarrhythmic role of endogenous late Na(+) current in the heart
    Lin Wu
    Pharmacological Sciences, Gilead Sciences, Palo Alto, California 94304, USA
    Am J Physiol Heart Circ Physiol 297:H1048-57. 2009
    ..Inhibition of this current partially reverses MAPD prolongation and abolishes arrhythmic activity caused by I(K) inhibitors...
  13. pmc Atrium-selective sodium channel block as a strategy for suppression of atrial fibrillation: differences in sodium channel inactivation between atria and ventricles and the role of ranolazine
    Alexander Burashnikov
    Masonic Medical Research Laboratory, Utica, NY 13501, USA
    Circulation 116:1449-57. 2007
    ..The development of selective atrial antiarrhythmic agents is a current strategy for suppression of atrial fibrillation (AF)...
  14. pmc Late sodium current contributes to diastolic cell Ca2+ accumulation in chronic heart failure
    Nidas A Undrovinas
    Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202 2689, USA
    J Physiol Sci 60:245-57. 2010
    ..We conclude that INaL contributes to diastolic Ca2+ accumulation and spontaneous Ca2+ release in HF...
  15. ncbi Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, NaV1.8
    Josephine Lai
    Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA
    Pain 95:143-52. 2002
    ..These data provide direct evidence linking NaV1.8 to neuropathic pain. As NaV1.8 expression is restricted to sensory neurons, this channel offers a highly specific and effective molecular target for the treatment of neuropathic pain...
  16. ncbi Presynaptic Na+ channels: locus, development, and recovery from inactivation at a high-fidelity synapse
    Ricardo M Leão
    The Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239 3098, USA
    J Neurosci 25:3724-38. 2005
    ..We propose that the high density and polarized locus of Na+ channels on a long heminode are critical design features that allow the mature calyx of Held terminal to fire reliably at frequencies near 1 kHz...
  17. pmc Subcellular heterogeneity of sodium current properties in adult cardiac ventricular myocytes
    Xianming Lin
    Leon H Charney Division of Cardiology, New York University School of Medicine, New York, New York 10016, USA
    Heart Rhythm 8:1923-30. 2011
    ..Sodium channel α-subunits in ventricular myocytes (VMs) segregate either to the intercalated disc or to lateral membranes, where they associate with region-specific molecules...
  18. ncbi Mechanisms of atrial fibrillation termination by rapidly unbinding Na+ channel blockers: insights from mathematical models and experimental correlates
    Philippe Comtois
    Department of Medicine and Research Center, Montreal Heart Institute and Universite de Montreal, Montreal, Canada
    Am J Physiol Heart Circ Physiol 295:H1489-504. 2008
    ..These results provide new insights into the mechanisms by which rapidly unbinding class I antiarrhythmic agents, a class including several novel compounds of considerable promise, terminate AF...
  19. ncbi A novel conotoxin from Conus striatus, mu-SIIIA, selectively blocking rat tetrodotoxin-resistant sodium channels
    Cheng Zhong Wang
    Key Laboratory of Proteomics, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    Toxicon 47:122-32. 2006
    ....
  20. pmc On the relationship between block of the cardiac Na⁺ channel and drug-induced prolongation of the QRS complex
    A R Harmer
    Safety Assessment UK, AstraZeneca R and D Alderley Park, Macclesfield, UK
    Br J Pharmacol 164:260-73. 2011
    ..However, interpretation of hNa(v) 1.5 blocking potency requires knowledge of how hNa(v) 1.5 block translates into prolongation of the QRS complex...
  21. pmc Early blockade of injured primary sensory afferents reduces glial cell activation in two rat neuropathic pain models
    W Xie
    Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267 0531, USA
    Neuroscience 160:847-57. 2009
    ..We tested effects of locally inhibiting sensory neuron activity with sodium channel blockers on satellite glial cell activation in a rat spinal nerve ligation (SNL) model...
  22. pmc Contribution of voltage-gated sodium channels to the b-wave of the mammalian flash electroretinogram
    Deb Kumar Mojumder
    College of Optometry, University of Houston, 505 J Davis Armistead Bldg, 4901 Calhoun Road, Houston, TX 77204 2020, USA
    J Physiol 586:2551-80. 2008
    ..These findings indicate that activation of Na(v) channels in ON cone bipolar cells affects the b-wave of the rat ERG and must be considered when analysing results of ERG studies of retinal function...
  23. pmc Voltage-gated Sodium Channel Activity Promotes Cysteine Cathepsin-dependent Invasiveness and Colony Growth of Human Cancer Cells
    Ludovic Gillet
    INSERM U921, Nutrition, Croissance et Cancer, and INSERM U618, Protéases et Vectorisation Pulmonaires, Universite Francois Rabelais, FacultédeMédecine, 37032 Tours, France
    J Biol Chem 284:8680-91. 2009
    ..This general mechanism could lead to the identification of new targets allowing the therapeutic prevention of metastases...
  24. ncbi Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels
    Stephan A Pless
    Department of Anesthesiology, University of British Columbia, 2350 Health Science Mall, Vancouver, British Columbia, V6T 1Z3 Canada
    Nat Commun 2:351. 2011
    ..Our data shed new light on drug-target interactions underlying the inhibition of cardiac sodium channels by clinically relevant drugs and provide information for the directed design of AADs...
  25. ncbi Scorpion toxins specific for Na+-channels
    L D Possani
    Department of Molecular Recognition and Structural Biology, Institute of Biotechnology, National Autonomous University of Mexico, Avenida Universidad 2001, Cuernavaca, Mexico
    Eur J Biochem 264:287-300. 1999
    ..The presence of an intron at the DNA level, situated in the middle of the signal peptide, has been demonstrated...
  26. pmc Nonequilibrium calcium dynamics regulate the autonomous firing pattern of rat striatal cholinergic interneurons
    Joshua A Goldberg
    Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249, USA
    J Neurosci 29:8396-407. 2009
    ..During irregular firing, calcium entry at both timescales can be detected, suggesting that an interaction between the medium and slow calcium-dependent afterhyperpolarizations may underlie this firing pattern...
  27. pmc GTP-induced tetrodotoxin-resistant Na+ current regulates excitability in mouse and rat small diameter sensory neurones
    Mark D Baker
    Molecular Nociception Group, Department of Biology, Medawar Building, University College London, Gower Street, UK
    J Physiol 548:373-82. 2003
    ..These findings suggest that regulation of the persistent current has important consequences for nociceptor excitability...
  28. ncbi Electrostatic contributions of aromatic residues in the local anesthetic receptor of voltage-gated sodium channels
    Christopher A Ahern
    Department of Molecular Physiology and Biophysics, Institute of Hyperexcitability, Jefferson Medical College, Philadelphia, PA, USA
    Circ Res 102:86-94. 2008
    ..These results fine tune our understanding of local anesthetic inhibition of voltage-gated sodium channels and will help the design of safer and more salutary therapeutic agents...
  29. ncbi A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs
    Carmen R Valdivia
    Department of Medicine and Physiology, University of Wisconsin, Madison, WI, USA
    Cardiovasc Res 62:53-62. 2004
    ..Mutations in SCN5A cause arrhythmia syndromes including Brugada syndrome (BrS) and congenital long QT syndrome subtype 3 (LQT3). Here, we report a trafficking defective BrS-causing SCN5A mutation that was drug-rescued...
  30. ncbi Functional expression of voltage-gated sodium channels in primary cultures of human cervical cancer
    Daniel Diaz
    Departamento de Biofisica, Instituto de Fisiologia Celular, Universidad Nacional Autónoma de México México, DF, Mexico
    J Cell Physiol 210:469-78. 2007
    ..The results show for the first time the functional expression of VGSC in primary cultures from human CaC, and suggest that these channels might be considered as potential molecular markers for this type of cancer...
  31. pmc Alpha-scorpion toxin impairs a conformational change that leads to fast inactivation of muscle sodium channels
    Fabiana V Campos
    Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA
    J Gen Physiol 132:251-63. 2008
    ..These results are consistent with the proposed model, in which Ts3 specifically impairs the fraction of the movement of the S4-DIV that allows fast inactivation to occur at normal rates...
  32. ncbi SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes
    Caroline R Fertleman
    Department of Paediatrics and Child Health, Royal Free and University College Medical School, University College London, 5 University Street, London WC1E 6JJ, United Kingdom
    Neuron 52:767-74. 2006
    ..PEPD and PE are allelic variants with distinct underlying biophysical mechanisms and represent a separate class of peripheral neuronal sodium channelopathy...
  33. pmc Ranolazine selectively blocks persistent current evoked by epilepsy-associated Naν1.1 mutations
    Kristopher M Kahlig
    Department of Pharmacology, Vanderbilt University, Nashville, TN 37232 0275, USA
    Br J Pharmacol 161:1414-26. 2010
    ..Here, we investigated the ability of ranolazine to preferentially inhibit increased persistent current evoked by mutant Na(V) 1.1 channels...
  34. ncbi Voltage-gated sodium channel blockers; target validation and therapeutic potential
    John N Wood
    Molecular Nociception Group, Biology UCL, Gower Street, London WC1 E 6BT
    Curr Top Med Chem 5:529-37. 2005
    ..They underlie electrical signalling in nerve and muscle. It has long been known that sodium channel blockers are anaesthetics as well as powerful analgesics when delivered at low concentrations...
  35. ncbi Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: I. Lateral motility
    S P Fraser
    Imperial College of Science, Technology, and Medicine, Department of Biological Sciences, Sir Alexander Fleming Building, Imperial College Road, London, United Kingdom
    J Cell Physiol 195:479-87. 2003
    ..The results, taken together, would suggest strongly that functional VGSC expression enhances cellular motility of PCa cells. The relevance of these findings to the metastatic process in PCa is discussed...
  36. pmc Two types of cone bipolar cells express voltage-gated Na+ channels in the rat retina
    Jinjuan Cui
    Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    Vis Neurosci 25:635-45. 2008
    ..Multiple spike-like potentials were also observed in some of these cells. Results of this study provide valuable insights into the function of voltage-gated Na+ channels of retinal bipolar cells in retinal processing...
  37. ncbi Transcriptional and functional profiles of voltage-gated Na(+) channels in injured and non-injured DRG neurons in the SNI model of neuropathic pain
    Temugin Berta
    Department of Anesthesiology, University Hospital Center and University of Lausanne, CH 1011 Lausanne, Switzerland
    Mol Cell Neurosci 37:196-208. 2008
    ..Our results describe altered neuronal electrogenesis following SNI that is likely induced by a complex regulation of VGSCs...
  38. pmc Electrostatic and steric contributions to block of the skeletal muscle sodium channel by mu-conotoxin
    Kwokyin Hui
    Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1
    J Gen Physiol 119:45-54. 2002
    ....
  39. ncbi Ion channels associated with the ectopic discharges generated after segmental spinal nerve injury in the rat
    X Liu
    Marine Biomedical Institute, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1069, USA
    Brain Res 900:119-27. 2001
    ....
  40. ncbi Voltage-gated Na+ channels: multiplicity of expression, plasticity, functional implications and pathophysiological aspects
    J K J Diss
    Neuroscience Solutions to Cancer Research Group, Department of Biological Sciences, Imperial College London, South Kensington Campus, Imperial College Road, London, SW7 2AZ, UK
    Eur Biophys J 33:180-93. 2004
    ....
  41. pmc A Nav1.7 channel mutation associated with hereditary erythromelalgia contributes to neuronal hyperexcitability and displays reduced lidocaine sensitivity
    Patrick L Sheets
    Department of Pharmacology and Toxicology, Stark Neurosciences Research Institute, Indiana University School of Medicine, 950 West Walnut St, R2 468, Indianapolis, IN 46202, USA
    J Physiol 581:1019-31. 2007
    ..7 and suggests that the response of individuals with hereditary erythromelalgia to lidocaine treatment may be determined, at least in part, by their specific genotype...
  42. pmc Targeting of sodium channel blockers into nociceptors to produce long-duration analgesia: a systematic study and review
    D P Roberson
    FM Kirby Neurobiology Center and Department of Neurology, Children s Hospital, Boston, MA 02115, USA
    Br J Pharmacol 164:48-58. 2011
    ..This involves co-administration of QX-314 and a TRPV1 agonist to produce a long-lasting local analgesia. For potential clinical use we propose using lidocaine as the TRPV1 agonist, because it activates TRPV1 at clinical doses...
  43. ncbi RSD1235 blocks late INa and suppresses early afterdepolarizations and torsades de pointes induced by class III agents
    Peter M R Orth
    Cardiome Pharma Corporation, 6th Floor, Vancouver BC, Canada
    Cardiovasc Res 70:486-96. 2006
    ..Further, RSD1235's ability to reverse the pro-arrhythmic actions of the class III agents dofetilide and clofilium was assessed in isolated Purkinje fibers and an in vivo model of torsades de pointes (TdP)...
  44. ncbi Zonisamide versus topiramate in migraine prophylaxis: a double-blind randomized clinical trial
    Seyed Ehsan Mohammadianinejad
    Department of Neurology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
    Clin Neuropharmacol 34:174-7. 2011
    ....
  45. ncbi The relationship between sodium channel inhibition and anticonvulsant activity in a model of generalised seizure in the rat
    Charles H Large
    epartment of Molecular and Cellular Biology, Neuroscience Centre of Excellence for Drug Discovery, Medicines Research Centre, GlaxoSmithKline S p A, Via Fleming 4, Verona 37135, Italy
    Epilepsy Res 85:96-106. 2009
    ..We found that a higher unbound concentration of the drug in the brain was required for anticonvulsant efficacy than would be expected given its sodium channel blocking potency...
  46. ncbi Na(v)1.5 sodium channels in a human microglial cell line
    E Nicholson
    MRC Centre for Synaptic Plasticity, University of Bristol, School of Medical Sciences, Bristol, BS8 1TD, UK
    J Neuroimmunol 215:25-30. 2009
    ..The presence of the Na(V)1.5 subunit in microglial cells is discussed with respect to its reported roles in phagocytosis, proliferation and migration of other non-cardiac cells...
  47. ncbi The pharmacological response of ischemia-related atrial fibrillation in dogs: evidence for substrate-specific efficacy
    Lena Rivard
    Research Center and Department of Medicine, Montreal Heart Institute, Universite de Montreal, Montreal, Canada
    Cardiovasc Res 74:104-13. 2007
    ..The present study assessed the effects of class 1-4 antiarrhythmic-drugs on the electrophysiological consequences of acute atrial ischemia, and compared effects in ischemic AF with those in vagal AF...
  48. pmc Bidirectional modulation of isoflurane potency by intrathecal tetrodotoxin and veratridine in rats
    Y Zhang
    Department of Anesthesiology, Fuwai Hospital and Cardiovascular Institute, Beijing, China
    Br J Pharmacol 159:872-8. 2010
    ....
  49. ncbi Molecular design of new sodium channel blockers
    Ping Li
    Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, China
    Biochem Biophys Res Commun 414:321-5. 2011
    ..This work will enhance our understanding of the molecular determinants of toxins affecting VGSCs and aid the rational design of subtype-specific blockers of the channels...
  50. ncbi Sodium current in human intestinal interstitial cells of Cajal
    Peter R Strege
    Enteric Neuroscience Program, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA
    Am J Physiol Gastrointest Liver Physiol 285:G1111-21. 2003
    ..A mechanosensitive Na+ channel current is present in human intestinal ICC and appears to play a role in the control of intestinal motor function...
  51. ncbi A selective Nav1.8 sodium channel blocker, A-803467 [5-(4-chlorophenyl-N-(3,5-dimethoxyphenyl)furan-2-carboxamide], attenuates spinal neuronal activity in neuropathic rats
    Steve McGaraughty
    Neuroscience Research, Abbott Laboratories, R4PM, AP9 1, 100 Abbott Park Rd, Abbott Park, IL 60064 6118, USA
    J Pharmacol Exp Ther 324:1204-11. 2008
    ..However, Na(v)1.8 sodium channels on central terminals seem to be key to the modulation of spontaneous firing in SNL rats...
  52. pmc Acid solution is a suitable medium for introducing QX-314 into nociceptors through TRPV1 channels to produce sensory-specific analgesic effects
    He Liu
    Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China
    PLoS ONE 6:e29395. 2011
    ....
  53. ncbi Trafficking defects and gating abnormalities of a novel SCN5A mutation question gene-specific therapy in long QT syndrome type 3
    Yanfei Ruan
    Cardiovascular Genetics Program, Leon H Charney Division of Cardiology, New York University School of Medicine, New York, NY, USA
    Circ Res 106:1374-83. 2010
    b>Sodium channel blockers are used as gene-specific treatments in long-QT syndrome type 3, which is caused by mutations in the sodium channel gene (SCN5A). Response to treatment is influenced by biophysical properties of mutations.
  54. pmc Mechanisms of atrial-selective block of Na⁺ channels by ranolazine: I. Experimental analysis of the use-dependent block
    Andrew C Zygmunt
    Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13501, USA
    Am J Physiol Heart Circ Physiol 301:H1606-14. 2011
    ....
  55. pmc Block of wild-type and inactivation-deficient cardiac sodium channels IFM/QQQ stably expressed in mammalian cells
    A O Grant
    Departments of Medicine and Pediatrics, Duke University, Durham, NC 27706, USA
    Biophys J 79:3019-35. 2000
    ..The qualitative differences in use-dependent block appear to be the result of differences in drug dissociation rate. The inactivation gate may play a trapping role during exposure to some sodium channel blocking drugs...
  56. ncbi Effects of pre-emptive drug treatment on astrocyte activation in the cuneate nucleus following rat median nerve injury
    Jiann Jy Chen
    Department of Medical Research, Tao Yuan General Hospital, Taoyuan, Taiwan
    Pain 148:158-66. 2010
    ..In conclusion, suppressing reactions to injury, such as the generation of ectopic discharges and activation of NMDA receptors, can decrease astrocyte activation in the CN and attenuate neuropathic pain sensations...
  57. pmc Sodium channel molecular conformations and antiarrhythmic drug affinity
    Michael F Sheets
    University of Utah, The Nora Eccles Harrison Cardiovascular Research and Teaching Institute, Department of Internal Medicine, Salt Lake City, UT 84112, USA
    Trends Cardiovasc Med 20:16-21. 2010
    ....
  58. pmc Synthesis and evaluation of hermitamides A and B as human voltage-gated sodium channel blockers
    Eliseu O De Oliveira
    Drug Discovery Program, Department of Oncology, Georgetown University Medical Center, Washington, DC 20057, USA
    Bioorg Med Chem 19:4322-9. 2011
    ..We also present a potential binding mode for (S)-hermitamide B in the BTX-binding site and electrophysiology showing that these compounds are potent blockers of the hNav1.2 voltage-gated sodium channel...
  59. ncbi Point mutations at N434 in D1-S6 of mu1 Na(+) channels modulate binding affinity and stereoselectivity of local anesthetic enantiomers
    C Nau
    Department of Anesthesia Research Laboratories, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Mol Pharmacol 56:404-13. 1999
    ..We propose that in inactivated channels, residue mu1-N434 interacts directly with the positively charged moiety of LAs and that D1-S6 and D4-S6 form a domain-interface site for binding of BTX and LAs in close proximity...
  60. ncbi Effects of a new potent analog of tocainide on hNav1.7 sodium channels and in vivo neuropathic pain models
    C Ghelardini
    Department of Preclinical and Clinical Pharmacology, Faculty of Pharmacy, University of Florence, Florence, Italy
    Neuroscience 169:863-73. 2010
    ..Overall, these results indicate NeP1 as a new promising lead compound for further development in the treatment of chronic pain of neuropathic origin...
  61. ncbi Block of Na+ currents and suppression of action potentials in embryonic rat dorsal root ganglion neurons by ranolazine
    Ryoko Hirakawa
    Department of Biology, Gilead Sciences Inc, 1651 Page Mill Road, Palo Alto, CA 94304, USA
    Neuropharmacology 62:2251-60. 2012
    ....
  62. pmc Ethanol enhances glutamate transmission by retrograde dopamine signaling in a postsynaptic neuron/synaptic bouton preparation from the ventral tegmental area
    Chunyu Deng
    Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103 2714, USA
    Neuropsychopharmacology 34:1233-44. 2009
    ..Furthermore, ethanol stimulation of a single dopaminergic neuron is capable of eliciting the release of somatodendritic dopamine, which is sufficient to influence glutamatergic transmission at individual synapses...
  63. ncbi Substituted biaryl pyrazoles as sodium channel blockers
    Sriram Tyagarajan
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:5480-3. 2010
    ..A series of low molecular weight biaryl substituted pyrazole carboxamides were identified with good in-vitro potency and in-vivo efficacy. Compound 26, a Nav1.7 blocker has excellent efficacy in the Chung model of neuropathic pain...
  64. ncbi Animal peptides targeting voltage-activated sodium channels
    Bert Billen
    Laboratory of Toxicology, KULeuven, Campus Gasthuisberg O and N 2, PO Box 922, Herestraat 49, 3000 Leuven, Belgium
    Curr Pharm Des 14:2492-502. 2008
    ..This review puts venom peptides from spiders, scorpions and cone snails that target voltage-activated sodium channels in the spotlight, and addresses their potential therapeutical applications...
  65. ncbi Glucose stimulates glucagon release in single rat alpha-cells by mechanisms that mirror the stimulus-secretion coupling in beta-cells
    Hervør Lykke Olsen
    Lilly Research Laboratories, Essener Bogen 7, D 22419 Hamburg, Germany
    Endocrinology 146:4861-70. 2005
    ..The stimulatory action of glucose in isolated alpha-cells contrasts with the suppressive effect of the sugar in intact islets and highlights the primary importance of islet paracrine signaling in the regulation of glucagon release...
  66. pmc A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat
    Michael F Jarvis
    Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064, USA
    Proc Natl Acad Sci U S A 104:8520-5. 2007
    ..These data demonstrate that acute and selective pharmacological blockade of Na(v)1.8 sodium channels in vivo produces significant antinociception in animal models of neuropathic and inflammatory pain...
  67. ncbi Structure/function characterization of micro-conotoxin KIIIA, an analgesic, nearly irreversible blocker of mammalian neuronal sodium channels
    Min Min Zhang
    Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA
    J Biol Chem 282:30699-706. 2007
    ..need exists for the discovery and development of novel non-opioid analgesics, such as subtype-selective sodium channel blockers. Micro-conotoxin KIIIA is representative of micro-conopeptides previously characterized as inhibitors of ..
  68. pmc Effects of tetrodotoxin on the mammalian cardiovascular system
    Thomas Zimmer
    Institute of Physiology II, Friedrich Schiller University, Kollegiengasse 9, 07743 Jena, Germany
    Mar Drugs 8:741-62. 2010
    ..Altogether, these data strongly suggest that TTX sensitive Na+ channels, detected more recently in various heart tissues, are not involved in excitation phenomena in the healthy adult heart of higher mammals...
  69. ncbi Sodium channel activity modulates multiple functions in microglia
    Joel A Black
    Department of Neurology and Center for Neuroscience and Regeneration Research, Yale School of Medicine, New Haven, Connecticut 06518, USA
    Glia 57:1072-81. 2009
    ..6) indicate that Nav1.6 plays a role in microglial migration. The results demonstrate that the activity of sodium channels contributes to effector roles of activated microglia...
  70. ncbi Inhibition of tetrodotoxin (TTX)-resistant and TTX-sensitive neuronal Na(+) channels by the secretolytic ambroxol
    Thomas Weiser
    Department CNS Research, Boehringer Ingelheim Pharma KG, Ingelheim, Germany
    Mol Pharmacol 62:433-8. 2002
    ..g., lidocaine or benzocaine), the potency for Na(+) channel block was relatively high. A recent clinical trial has further confirmed that ambroxol relieved pain and was beneficial in patients who suffered from sore throat...
  71. ncbi Interaction between voltage-gated sodium channels and the neurotoxin, tetrodotoxin
    Chong Hyun Lee
    School of Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada
    Channels (Austin) 2:407-12. 2008
    ..We here review the properties of sodium channels and their interaction with TTX, and look at some special examples of TTX resistant channels wherein the benefit of toxin resistance may be offset by other behavioral costs...
  72. pmc Nociceptors are interleukin-1beta sensors
    Alexander M Binshtok
    Neural Plasticity Research Group, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 28:14062-73. 2008
    ..By acting as an IL-1beta sensor, nociceptors can directly signal the presence of ongoing tissue inflammation...
  73. pmc Mechanisms underlying the early phase of spike frequency adaptation in mouse spinal motoneurones
    G B Miles
    Department of Anatomy and Neurobiology, Dalhousie University, Halifax, NS, Canada
    J Physiol 566:519-32. 2005
    ..The removal of slow inactivation from this model was sufficient to remove SFA. These data indicate that slow inactivation of the fast, inactivating Na+ conductance is likely to be the key mechanism underlying early SFA in spinal MNs...
  74. pmc Late sodium current is a new therapeutic target to improve contractility and rhythm in failing heart
    Albertas Undrovinas
    Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202 2689, USA
    Cardiovasc Hematol Agents Med Chem 6:348-59. 2008
    ..g. Ca(2+)- or cytoskeleton- dependent) mechanisms of I(NaL) function...
  75. ncbi Comparative neuroprotective effect of sodium channel blockers after experimental spinal cord injury
    Ozkan Ates
    Inonu University, School of Medicine, Department of Neurosurgery, Turgut Ozal Medical Center, 44069 Malatya, Turkey
    J Clin Neurosci 14:658-65. 2007
    ..Previous studies have shown that some voltage-sensitive sodium channel blockers provide powerful neuroprotection...
  76. ncbi Two tarantula peptides inhibit activation of multiple sodium channels
    Richard E Middleton
    Department of Ion Channels, Merck Research Laboratories, Rahway, New Jersey, USA
    Biochemistry 41:14734-47. 2002
    ..1 channels with 10-fold less potency than its potency on Na(V) channels. These peptides represent novel tools for exploring the gating mechanisms of several Na(V) and Ca(V) channels...
  77. ncbi Voltage-gated sodium channels in neurological disorders
    Mohamed Chahine
    Le Centre de recherches Université Laval Robert Griffard, Quebec City, Guebec, Canada
    CNS Neurol Disord Drug Targets 7:144-58. 2008
    ..This review describes the biochemical, biophysical and pharmacological properties of neuronal voltage-gated sodium channels (VGSC) and their implication in several neurological disorders...
  78. ncbi Lidocaine suppresses subthreshold oscillations by inhibiting persistent Na(+) current in injured dorsal root ganglion neurons
    H Dong
    Institute of Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi an, Shaanxi, China
    Physiol Res 57:639-45. 2008
    ..Low concentration of lidocaine (10 micromol/l) suppresses SMPO by selectively inhibiting I(NaP), but not I(NaT), in chronically compressed DRG neurons...
  79. ncbi The role of sodium channels in neuropathic pain
    Marc Rogers
    Xention Ltd, Iconix Park, Pampisford, Cambridge CB2 4EF, United Kingdom
    Semin Cell Dev Biol 17:571-81. 2006
    ..One of the future challenges in the development of novel sodium channel blockers is to design and synthesise isoform-selective channel inhibitors...
  80. pmc Chinese-scorpion (Buthus martensi Karsch) toxin BmK alphaIV, a novel modulator of sodium channels: from genomic organization to functional analysis
    Zhi fang Chai
    Graduate School of the Chinese Academy of Sciences, Shanghai Institute of Physiology, Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People s Republic of China
    Biochem J 399:445-53. 2006
    ....
  81. ncbi Proximal persistent Na+ channels drive spike afterdepolarizations and associated bursting in adult CA1 pyramidal cells
    Cuiyong Yue
    Department of Physiology, Institute of Medical Sciences, Hebrew University Hadassah Faculty of Medicine, Jerusalem 91120, Israel
    J Neurosci 25:9704-20. 2005
    ..Through this action, proximal INaP critically determines the firing mode and spike output of adult CA1 pyramidal cells...
  82. ncbi Voltage-gated sodium channels: therapeutic targets for pain
    Sulayman D Dib-Hajj
    Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06520 8018, USA
    Pain Med 10:1260-9. 2009
    ..To provide an overview of the role of voltage-gated sodium channels in pathophysiology of acquired and inherited pain states, and of recent developments that validate these channels as therapeutic targets for treating chronic pain...
  83. ncbi Exploring the obscure profiles of pharmacological binding sites on voltage-gated sodium channels by BmK neurotoxins
    Zhi Rui Liu
    Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, China
    Protein Cell 2:437-44. 2011
    ....
  84. ncbi Voltage-gated sodium channels and hyperalgesia
    Josephine Lai
    Departments of Pharmacology, University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA
    Annu Rev Pharmacol Toxicol 44:371-97. 2004
    ..Many types of pain appear to reflect neuronal hyperexcitability, and importantly, use-dependent sodium channel blockers are effective in the treatment of many types of chronic pain...
  85. ncbi Increased persistent sodium current determines cortical hyperexcitability in a genetic model of amyotrophic lateral sclerosis
    Massimo Pieri
    Department of Neuroscience, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
    Exp Neurol 215:368-79. 2009
    ....
  86. ncbi Sodium channels in transient retinal bipolar cells enhance visual responses in ganglion cells
    Tomomi Ichinose
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 25:1856-65. 2005
    ..Our results suggest that bipolar cell sodium channels augment transient signals and contribute to the temporal segregation of visual information...
  87. pmc Coordinated changes in dendritic arborization and synaptic strength during neural circuit development
    Yi Rong Peng
    Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    Neuron 61:71-84. 2009
    ....
  88. pmc Cooccupancy of the outer vestibule of voltage-gated sodium channels by micro-conotoxin KIIIA and saxitoxin or tetrodotoxin
    Min Min Zhang
    Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA
    J Neurophysiol 104:88-97. 2010
    ..The demonstration that two interacting ligands ("syntoxins") occupy adjacent sites raises the possibility of evolving a much more sophisticated neuropharmacology of VGSCs...
  89. ncbi The discovery and characterization of a proton-gated sodium current in rat retinal ganglion cells
    Sarah Lilley
    Neural Injury and Repair Group, Centre for Neuroscience Research, King s College London, Guy s Campus, London, SE1 1UL, United Kingdom
    J Neurosci 24:1013-22. 2004
    ..The presence of a proton-gated current in the neural retina suggests that ASICs may have a more diverse role in the CNS...
  90. pmc μ-conotoxin KIIIA derivatives with divergent affinities versus efficacies in blocking voltage-gated sodium channels
    Min Min Zhang
    Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA
    Biochemistry 49:4804-12. 2010
    ....
  91. pmc Navβ subunits modulate the inhibition of Nav1.8 by the analgesic gating modifier μO-conotoxin MrVIB
    Michael J Wilson
    Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112, USA
    J Pharmacol Exp Ther 338:687-93. 2011
    ..Our results raise the possibility that μO-conotoxins and perhaps other gating modifiers may provide a means to functionally assess the β-subunit composition of VGSC complexes in neurons...
  92. ncbi Isoflurane and propofol inhibit voltage-gated sodium channels in isolated rat neurohypophysial nerve terminals
    Wei Ouyang
    Department of Anesthesiology, Box 50, LC 203, 525 E 68th St, Weill Medical College of Cornell University, New York, NY 10021, USA
    Mol Pharmacol 64:373-81. 2003
    ..Inhibition of voltage-gated Na+ channels may contribute to the presynaptic effects of general anesthetics on nerve terminal excitability and neurotransmitter release...
  93. ncbi Tetrodotoxin-resistant Na+ channels in human neuroblastoma cells are encoded by new variants of Nav1.5/SCN5A
    Shao Wu Ou
    Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8 35 1 Sakuragaoka, Kagoshima 890 8544, Japan
    Eur J Neurosci 22:793-801. 2005
    ..The IC50 for the TTX block was approximately 8 microM in both variants. These results suggest that SCN5A has a newly identified exon for alternative splicing and is more widely expressed than previously thought...
  94. ncbi Binding of sodium channel inhibitors to hyperpolarized and depolarized conformations of the channel
    N Lenkey
    Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, P O B 67, H 1450 Budapest, Hungary
    Neuropharmacology 60:191-200. 2011
    ....
  95. pmc Evaluation of the pharmacological activity of the major mexiletine metabolites on skeletal muscle sodium currents
    M De Bellis
    Unit of Pharmacology, Department of Pharmacobiology, University of Bari, Bari, Italy
    Br J Pharmacol 149:300-10. 2006
    ..It is extensively metabolized in humans but little information exists about the pharmacodynamic properties of its metabolites...
  96. ncbi The mechanism of intrinsic amplification of hyperpolarizations and spontaneous bursting in striatal cholinergic interneurons
    Charles J Wilson
    Department of Biology, University of Texas at San Antonio, 6900 North Loop, 1604 West, San Antonio, Texas 78249, USA
    Neuron 45:575-85. 2005
    ....
  97. ncbi Blocking acid-sensing ion channel 1 alleviates Huntington's disease pathology via an ubiquitin-proteasome system-dependent mechanism
    Hon Kit Wong
    Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    Hum Mol Genet 17:3223-35. 2008
    ..In conclusion, we believe that chemical compounds that target ASIC1a or pharmacological alleviation of UPS inhibition would be an effective and promising approach to combat HD and other polyQ-related disorders...
  98. ncbi Inhibition of membrane Na+ channels by A type botulinum toxin at femtomolar concentrations in central and peripheral neurons
    Min Chul Shin
    Research Division for Life Sciences, Kumamoto Health Science University, Japan
    J Pharmacol Sci 118:33-42. 2012
    ..The results suggest evidently that A2NTX could be also used as a powerful drug in treating epilepsy and several types of pain...
  99. ncbi Ranolazine: an antianginal drug with antiarrhythmic properties
    Juan Tamargo
    Department of Pharmacology, School of Medicine, Universidad Complutense, 28040 Madrid, Spain
    Expert Rev Cardiovasc Ther 9:815-27. 2011
    ..This article reviews the role of the I(NaL) and provides an update on experimental and clinical evidence supporting the efficacy and safety of ranolazine across a broad spectrum of arrhythmias...
  100. ncbi Clinical and electrocardiographic predictors of positive response to the intravenous sodium channel blockers in patients suspected of the Brugada syndrome
    Shahab Shahrzad
    Cardiac Electrophysiology Research Center, Rajaie Cardiovascular Medical and Research Center, Tehran University of Medical Sciences, Tehran, Iran
    Int J Cardiol 165:285-90. 2013
    b>Sodium channel blockers are used to unmask the diagnostic ECG pattern of the Brugada syndrome (BrS) in case of a non-diagnostic baseline ECG...
  101. ncbi Effects of the NA+ channel blocker pilsicainide on the electrophysiologic properties of pulmonary veins in patients with atrial fibrillation
    Koichiro Kumagai
    Department of Cardiology, Fukuoka University Hospital, Fukuoka, Japan
    J Cardiovasc Electrophysiol 15:1396-401. 2004
    ..The aim of the present study was to evaluate the effect of the pure Na+ channel blocker pilsicainide on the PVs...

Research Grants64

  1. Selective targeting of sodium channel blockers to pain-sensing neurons
    Bruce P Bean; Fiscal Year: 2012
    ..The overall goal of the proposed research is to identify combinations of TRPV1 activators and charged sodium channel blockers that optimize the block of excitability of nociceptive sensory neurons...
  2. Ion Selective Quantum Dots for Intracellular Mapping of Sodium Sparks in Cardiac
    Heather A Clark; Fiscal Year: 2012
    ..Sodium sparks will be identified in cardiac myocytes, and will be evaluated for effects to sodium channel blockers. PUBLIC HEALTH RELEVANCE: The ultimate goal of this application is to develop and use a new intracellular ..
  3. The Development Epithelial Sodium Channel Blockers for Chronic Dry Eye
    Benjamin Yerxa; Fiscal Year: 2011
    ..KCS/DED results from inadequate aqueous tear fluid on the eyes. Parion Sciences is developing a novel therapeutic agent that is predicted to provide long acting relief from dry eye symptoms. ..
  4. The Development Epithelial Sodium Channel Blockers for Chronic Dry Eye
    KARL H DONN; Fiscal Year: 2010
    ..KCS/DED often results from inadequate aqueous tear fluid on the eyes. Parion Sciences is developing a novel therapeutic agent that is predicted to provide long acting relief from dry eye symptoms. ..
  5. PROLONGED DURATION LOCAL ANESTHESIA
    Daniel S Kohane; Fiscal Year: 2013
    ..of this research is to develop particulate prolonged duration local anesthetics (PDLA) employing site 1 sodium channel blockers such as saxitoxin (STX)...
  6. MODULATION OF CARDIAC REPOLARIZATION
    Dan M Roden; Fiscal Year: 2013
    ..of sodium channel function predisposes to sudden death due to ventricular fibrillation: this is seen with sodium channel blockers in patients convalescing from acute myocardial infarction and with mutations that reduce cell surface ..
  7. Development of Novel Approaches for the Pharmacologic Treatment of Atrial Fibrill
    Charles Antzelevitch; Fiscal Year: 2013
    ..5) assess the effectiveness of different classes of sodium channel blockers in terminating and suppressing re-induction of AF, determine to what extent these agents are atrial-..
  8. Harnessing gating-pore currents to identify novel Nav1.7 modulators
    Theodore R Cummins; Fiscal Year: 2012
    ..However, although sodium channel blockers are useful for preventing acute pain, they are often associated with undesirable cardiac and CNS side ..
  9. DEVELOPMENT OF NOVEL ANTIEPILEPTIC DRUGS
    Manoj K Patel; Fiscal Year: 2010
    ..pharmacology that has been well documented in temporal lobe epilepsy, reducing the efficacy of the sodium channel blockers in suppressing epileptic seizures...
  10. Annulation Strategies Toward the Total Synthesis of Saxitoxin and Zetekitoxin AB
    Michael R Krout; Fiscal Year: 2011
    ..Guanidinium alkaloids saxitoxin and zetekitoxin AB are potent voltage-gated sodium channel blockers that pose significant synthetic challenges...
  11. MOLECULAR PHYSIOLOGY OF HYPERKALEMIC PERIODIC PARALYSIS
    Lawrence Hayward; Fiscal Year: 2001
    ..b>Sodium channel blockers or other drugs will be compared for effectiveness in preventing abnormal muscle excitation or ..
  12. CONOPEPTIDE SODIUM CHANNEL BLOCKERS FOR CHRONIC PAIN
    James Garrett; Fiscal Year: 2000
    ..4. Express various Na channels (PN3, SNS2, SkM1, BIIA [already on hand] and cardiac H1 [in process of obtaining]) in Xenopus oocytes and screen PN3-promising candidates for non-selectivity. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE ..
  13. DEVELOPMENT OF EPITHELIAL SODIUM CHANNEL BLOCKERS FOR CF
    Judith St George; Fiscal Year: 2006
    ..Ultimately, our goal is the full clinical development of 552-02 as a first line therapy for patients suffering from CF airways disease [unreadable] [unreadable]..
  14. PROLONGED DURATION LOCAL ANESTHESIA
    DANIEL KOHANE; Fiscal Year: 2004
    ..take advantage of synergistic interactions between conventional amino amide local anesthetics and site 1 sodium channel blockers, as well as the potentiating effect of adjuncts such as glucocorticoids...
  15. INTERACTION OF ISCHEMIA, DRUGS, AND RATE ON CONDUCTION
    Wayne Cascio; Fiscal Year: 1991
    ..aiNa, aiH+ and possibly aiCa++ at different stimulation rates both in the presence and absence of sodium channel blockers and simulated ischemia...
  16. NEUROTRANSMITTERS AND BRAIN INJURY
    MARK ZORNOW; Fiscal Year: 2000
    ..examine effects of agents that may attenuate EAA release, including N-type calcium channel antagonists, sodium channel blockers, and adenosine A1 agonists on MRI-derived indices of intracellular swelling, histologic outcome, and ..
  17. IONIC CURRENTS AND (CA++)I IN CORONARY SMOOTH MUSCLE
    James Johns; Fiscal Year: 1992
    ..currents using a model similar to that of the Modulated Receptor Hypothesis, to explain the action of sodium channel blockers. The proposed area of research is an important area from both a clinical and a basic science standpoint...
  18. THERAPEUTIC NA+ CHANNEL BLOCKERS: RECEPTOR & DRUG DESIGN
    GING WANG; Fiscal Year: 2007
    ..Such drugs, either taken orally or injected locally, may be beneficial for patients with chronic and intractable cancer pain. ..
  19. MOLECULAR BASIS OF LIGAND/SODIUM CHANNEL INTERACTIONS
    GING WANG; Fiscal Year: 2002
    ....
  20. RVM CCK and Neuropathic Pain
    Josephine Lai; Fiscal Year: 2007
    ..In this regard, the proposed experiments may reveal an important role for CCK receptor antagonists as therapy for neuropathic pain. ..
  21. PHARMACOLOGY OF CARDIAC SODIUM CHANNEL MODIFIERS
    Michael Sheets; Fiscal Year: 2008
    ..The results of these studies should improve our overall understanding of the molecular mechanisms of anti-arrhythmic drugs modification of cardiac Na channels. [unreadable] [unreadable]..
  22. SELECTIVE BLOCKADE OF TTX-R SODIUM CHANNELS FOR PAIN
    Josephine Lai; Fiscal Year: 2001
    ..These studies may have great practical significance towards the development of an effective therapy for neuropathic pain with few, or no, side effects. ..
  23. Afferent modulation in bladde dysfunction
    Naoki Yoshimura; Fiscal Year: 2007
    ..abstract not provided ..
  24. Development of isoform specific sensory neuronal sodium channel blockers
    THEODORE CUMMINS; Fiscal Year: 2008
    ..electrical activity of sensory neurons has been hindered by the lack of isoform specific neuronal sodium channel blockers. The goal of this R21 grant proposal is to develop selective sodium channel blockers based on biological ..
  25. Lower urinary tract dysfunction in Parkinson's disease
    Naoki Yoshimura; Fiscal Year: 2003
    ..This is a high priority in the urologic care of patients with Parkinson's disease. ..
  26. Dietary Omega-3 Fatty Acids and Sudden Cardiac Death
    GEORGE EDWARD BILLMAN; Fiscal Year: 2010
    ..This project will also determine the effectiveness of fish oil supplements in reducing sudden death due to a lethal abnormal heart rhythm after a heart attack. ..
  27. MOLECULAR MECHANISMS OF HEXACARBON-INDUCED AXON ATROPHY
    RICHARD LOPACHIN; Fiscal Year: 2009
    ..Understanding the role and mechanism of axon atrophy in solvent neurotoxicity has broad-based implications for human occupational health and risk assessment. ..
  28. Bladder Pain Gene Therapy with Pro-opiomelanocortin cDNA
    Naoki Yoshimura; Fiscal Year: 2004
    ..This research project is important to provide a solid basis for potential future clinical application. ..
  29. Mechanisms Underlying Rhythm Generation in Identified Spinal Interneurons in Mice
    Lea Ziskind Conhaim; Fiscal Year: 2010
    ....
  30. Neurophysiology and Biomechanics of Urethra in Stress Urinary Incontinence
    Naoki Yoshimura; Fiscal Year: 2008
    ..This is recognized as a high priority in the urologic/gynecologic care of SUI patients. [unreadable] [unreadable]..
  31. CARDIAC NA+ CHANNEL GATING AND LOCAL ANESTHETIC BLOCK
    STERLING WRIGHT; Fiscal Year: 2004
    ..abstract_text> ..
  32. AFFERENT PLASTICITY UNDERLYING URETHRAL AND PELVIC PAIN
    Naoki Yoshimura; Fiscal Year: 2010
    ..This is recognized as a high priority in the urologic care of patients with IC/CPPS. ..
  33. TRAINING IN MOLECULAR NEUROBIOLOGY
    William Catterall; Fiscal Year: 2008
    ..The training program will integrate the substantial expertise of this group of faculty in a coordinated pre-doctoral and post-doctoral training effort. ..
  34. Effect of Daily Exercise on Cardiac Autonomic Regulation
    GEORGE BILLMAN; Fiscal Year: 2005
    ..Ventricular contractile responses to Beta1- and Beta2-adrenoceptor stimulation will be examined in vivo by echocardiography and in vitro by single cell fluorescence microscopy/video edge detection. ..
  35. Mode of Action of Insecticides: Electrophysiological
    Toshio Narahashi; Fiscal Year: 2004
    ..This information will significantly contribute to the development of newer therapeutic means of insecticide intoxication of humans and of more effective and safer insecticides. ..
  36. CHARGED DIHYDROPYRIDINES--PROBES OF HEART CA++ CHANNELS
    Robert Kass; Fiscal Year: 2001
    ....
  37. Development of Sensory/Pain-Selective Local Anesthetics
    Peter Gerner; Fiscal Year: 2006
    ..abstract_text> ..
  38. Mechnaisms of Late Sodium Current in Failing Heart
    Albertas Undrovinas; Fiscal Year: 2006
    ..Knowledge derived from the present proposal may reveal novel targets for the treatment of life-threatening arrhythmias associated with chronic HF. ..
  39. Abused Inhalant Actions at GABA and Glutamate Synapses
    M MacIver; Fiscal Year: 2008
    ..Taken together, the results will allow a quantitative comparison of drug effects on glutamate and GABA-mediated transmission for commonly abused solvents including: toluene, 1,1,1-trichloroethane andtrichloroethylene. ..
  40. Automated Storage and Retrieval of Biological Systems
    Dan Roden; Fiscal Year: 2008
    ..Accordingly, this proposal requests a high end instrument to accomplish these goals, and to thereby enable a new era of Personalized Medicine. [unreadable] [unreadable] [unreadable] [unreadable]..
  41. ACUTE BRAIN INJURY, MECHANISMS AND PROTECTION
    John Olney; Fiscal Year: 2001
    ..The long term goals are to clarify the underlying mechanisms and develop improved methods of treating human pediatric acute brain injury conditions. ..
  42. NEUROBIOLOGICAL EFFECTS OF ALTERED MOTOR CONTROL IN REM
    LARRY SANFORD; Fiscal Year: 2001
    ..These studies may lead to a better understanding of disorders of REM, such as REM behavior disorder, which, like REM-A, is characterized by overt behavior during sleep. ..
  43. NEURAL MECHANISMS OF VENTRICULAR ELECTRICAL REMODELING
    Philip Adamson; Fiscal Year: 2003
    ..These clinically applicable interventions may modify the natural history of diseases, such as heart failure, characterized by ventricular electrical remodeling leading to a high risk for lethal arrhythmias. ..
  44. DEVELOPMENTAL BRAIN DAMAGE BY DRUGS OF ABUSE
    John W Olney; Fiscal Year: 2010
    ..abstract_text> ..
  45. NEURONAL ORGANIZATION OF BASAL GANGLIA
    Charles Wilson; Fiscal Year: 2003
    ..This latter will allow us to determine whether there is an actual mismatch between physiological and anatomical estimates of connectivity (i.e. non-functional synaptic connections). ..
  46. Glutamate Uptake & the Pathogenesis of Neuropathic Pain
    Jianren Mao; Fiscal Year: 2007
    ..abstract_text> ..
  47. Temporal Transcriptomes of TBI and OGD for Dissemination (T3OD)
    Barclay Morrison; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  48. Role of DEG/ENaC in the renal myogenic response
    NIKKI JERNIGAN; Fiscal Year: 2005
    ..abstract_text> ..
  49. NEURAL CIRCUITRY OF SENSORIMOTOR GATING ACROSS SPECIES
    Neal Swerdlow; Fiscal Year: 2006
    ....
  50. Renal Epithelial Sodium Channels and Syntaxins
    Sunil Saxena; Fiscal Year: 2006
    ..Epitope mapping will be used to optimize the specificity of polyclonal antibodies, and anti-sense oligonucleotides will be used to modulate the level of endogenous proteins in the mpkCCDC14 line. ..
  51. Regulation of ENaC by Serine Proteases in Airways
    Scott Donaldson; Fiscal Year: 2006
    ..The PI's long term goals are to provide important new insights into the basic elements of airway defense, CF lung disease, and to bring these findings to the development of novel therapies for CF lung disease. ..
  52. Neuroscience at the Boundaries of Neurology and Psychiatry
    Neal Swerdlow; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  53. Cerebellar Circuitry and Plasticity in an Electric Fish
    Victor Han; Fiscal Year: 2007
    ..The primary method will be whole-cell patch recordingin in vitro slices, combined with labelingof recorded elements for morphologicalidentification. ..
  54. A Simple Measure for Studying Sensory Gating Deficits
    Neal Swerdlow; Fiscal Year: 2007
    ..abstract_text> ..
  55. Inherited Ion Channel Defects in Arrhythmias
    AUGUSTUS GRANT; Fiscal Year: 2005
    ..Isoform expression will be determined by in situ hydridization. The proposed studies will provide new insights into ion channel function, their regulation and possible basis for cardiac arrhythmias. ..
  56. The Structure and Gating of the Epithelial Na+ Channel
    OSSAMA KASHLAN; Fiscal Year: 2005
    ..Such a map will help to delineate which amongst the currently proposed models for ENaC gating is most likely ..
  57. Membrane Transport of NH3 and NH4+
    NAZIH NAKHOUL; Fiscal Year: 2008
    ..These are new properties of NH3/NH4+ transport that will help explain the role of NH3 and NH4+ in acidosis and their effect on transport of other ions a well. ..
  58. Biologic Ventricular Assist Device
    Robert Kloner; Fiscal Year: 2004
    ..Identification and characterization of transplants will be carried out with PCR analysis of the Y chromosome (male cells into female host), detailed histologic analysis and immunostaining for muscle cell markers. ..
  59. MECHANISMS AND SITES OF VENTILATORY NEUROGENESIS
    WALTER ST JOHN; Fiscal Year: 2008
    ..Such information might provide insights into dysfunctions of the control of ventilation in humans, such as in "sleep apnea" or the "sudden infant death syndrome." [unreadable] [unreadable] [unreadable]..
  60. Inflammation-Induced Plasticity in Sensory Neurons
    Michael Gold; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  61. Development of an electrical diagnostic for melanoma
    Richard Nuccitelli; Fiscal Year: 2008
    ..If the handheld BFI is able to reliably detect malignant skin lesions, it will improve the quality of life for tens of thousands of dermatology patients in the United States alone. [unreadable] [unreadable] [unreadable]..
  62. MECHANISM OF INHIBITION OF CFTR BY AMP-ACTIVATED KINASE
    KENNETH HALLOWS; Fiscal Year: 2005
    ..A final goal is to extend the search for functional effects of AMPK to transport systems that are closely associated with and modulated by CFTR. ..