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Possible involvement of tetrodotoxin-resistant sodium channels in cough reflex.

Abstract
We examined the involvement of tetrodotoxin (TTX)-resistant sodium channels in the peripheral mechanisms of the cough reflex in mice. We also examined the possibility of using ambroxol as an effective antitussive agent, and found that it produced antitussive effects through the inhibition of TTX-resistant sodium channels. The inhalation of fenvalerate, at concentrations of 0.3, 1 and 3μg/ml, for 5min produced coughs in a concentration-dependent manner. Pretreatment with tetrodotoxin, at a dose of 1μg/kg, s.c., slightly but significantly reduced the number of fenvalerate (3μg/ml)-induced coughs. However, the number of fenvalerate-induced coughs in tetorodotoxin-treated mice was still significantly greater than those in vehicle (0.4% DMSO) alone inhaled mice. On the other hand, pretreatment with tetrodotoxin, at a dose of 1μg/kg, s.c., almost completely reduced the number of citric acid (0.25M)-induced coughs to the level in vehicle (saline) alone inhaled mice. Pretreatment with ambroxol, at doses of 10, 30, 100 and 300mg/kg, p.o., dose-dependently and significantly reduced the number of fenvalerate (3μg/ml)-induced coughs. The present findings indicate that TTX-resistant sodium channels may play an important role in the enhancement of C-fiber-mediated cough pathways. Furthermore, ambroxol may prove to be a useful cough suppressant.
AuthorsJunzo Kamei, Yuki Nakanishi, Yoko Ishikawa, Shun-Suke Hayashi, Megumi Asato, Masahiro Ohsawa
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 652 Issue 1-3 Pg. 117-20 (Feb 10 2011) ISSN: 1879-0712 [Electronic] Netherlands
PMID21130084 (Publication Type: Journal Article)
Copyright2010 Elsevier B.V. All rights reserved.
Chemical References
  • Antitussive Agents
  • Nitriles
  • Pyrethrins
  • Sodium Channels
  • Ambroxol
  • Tetrodotoxin
  • fenvalerate
Topics
  • Ambroxol (pharmacology, therapeutic use)
  • Animals
  • Antitussive Agents (pharmacology, therapeutic use)
  • Cough (chemically induced, drug therapy)
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nerve Fibers, Unmyelinated (drug effects, metabolism)
  • Nitriles
  • Pyrethrins
  • Sodium Channels (metabolism)
  • Tetrodotoxin (pharmacology, therapeutic use)

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