PMID- 19655117
OWN - NLM
STAT- MEDLINE
DCOM- 20091015
LR  - 20131121
IS  - 0171-2004 (Print)
IS  - 0171-2004 (Linking)
IP  - 194
DP  - 2009
TI  - The pharmacology of voltage-gated sodium channels in sensory neurones.
PG  - 519-61
LID - 10.1007/978-3-540-79090-7_15 [doi]
AB  - Voltage-gated sodium channels (VGSCs) are vital for the normal functioning of 
      most excitable cells. At least nine distinct functional subtypes of VGSCs are 
      recognized, corresponding to nine genes for their pore-forming alpha-subunits. 
      These have different developmental expression patterns, different tissue 
      distributions in the adult and are differentially regulated at the cellular level 
      by receptor-coupled cell signalling systems. Unsurprisingly, VGSC blockers are 
      found to be useful as drugs in diverse clinical applications where excessive 
      excitability of tissue leads to pathological dysfunction, e.g. epilepsy or 
      cardiac tachyarrhythmias. The effects of most clinically useful VGSC blockers are 
      use-dependent, i.e. their efficacy depends on channel activity. In addition, many 
      natural toxins have been discovered that interact with VGSCs in complex ways and 
      they have been used as experimental probes to study the structure and function of 
      the channels and to better understand how drugs interact with the channels. Here 
      we have attempted to summarize the properties of VGSCs in sensory neurones, 
      discuss how they are regulated by cell signalling systems and we have considered 
      briefly current concepts of their physiological function. We discuss in detail 
      how drugs and toxins interact with archetypal VGSCs and where possible consider 
      how they act on VGSCs in peripheral sensory neurones. Increasingly, drugs that 
      block VGSCs are being used as systemic analgesic agents in chronic pain 
      syndromes, but the full potential for VGSC blockers in this indication is yet to 
      be realized and other applications in sensory dysfunction are also possible. 
      Drugs targeting VGSC subtypes in sensory neurones are likely to provide novel 
      systemic analgesics that are tissue-specific and perhaps even disease-specific, 
      providing much-needed novel therapeutic approaches for the relief of chronic 
      pain.
FAU - Docherty, Reginald J
AU  - Docherty RJ
AD  - Neurorestoration Group, Wolfson CARD, King's College London, London SE1 9RT, UK. 
      reginald.docherty@kcl.ac.uk
FAU - Farmer, Clare E
AU  - Farmer CE
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Germany
TA  - Handb Exp Pharmacol
JT  - Handbook of experimental pharmacology
JID - 7902231
RN  - 0 (Analgesics)
RN  - 0 (Anesthetics, Local)
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 0 (Anticonvulsants)
RN  - 0 (Sodium Channel Blockers)
RN  - 0 (Sodium Channels)
RN  - 9NEZ333N27 (Sodium)
SB  - IM
MH  - Analgesics/pharmacology
MH  - Anesthetics, Local/pharmacology
MH  - Animals
MH  - Anti-Arrhythmia Agents/pharmacology
MH  - Anticonvulsants/pharmacology
MH  - Binding Sites
MH  - Chronic Disease
MH  - Humans
MH  - Ion Channel Gating/*drug effects
MH  - Membrane Potentials
MH  - Pain/metabolism/prevention & control
MH  - Sensory Receptor Cells/*drug effects/metabolism
MH  - Sodium/metabolism
MH  - Sodium Channel Blockers/metabolism/*pharmacology
MH  - Sodium Channels/*drug effects/metabolism
MH  - Syndrome
RF  - 249
EDAT- 2009/08/06 09:00
MHDA- 2009/10/16 06:00
CRDT- 2009/08/06 09:00
PHST- 2009/08/06 09:00 [entrez]
PHST- 2009/08/06 09:00 [pubmed]
PHST- 2009/10/16 06:00 [medline]
AID - 10.1007/978-3-540-79090-7_15 [doi]
PST - ppublish
SO  - Handb Exp Pharmacol. 2009;(194):519-61. doi: 10.1007/978-3-540-79090-7_15.