Possible involvement of tetrodotoxin-resistant sodium channels in cough reflex.
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.
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan. kamei@hoshi.ac.jp
Junzo
J
Kamei
Yuki
Y
Nakanishi
Yoko
Y
Ishikawa
Shun-Suke
SS
Hayashi
Megumi
M
Asato
Masahiro
M
Ohsawa
D000551:Ambroxol / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000378:metabolism; D009570:Nitriles; D011722:Pyrethrins; D015222:Sodium Channels / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology / Q000627:therapeutic use*
D000996:Antitussive Agents; D009570:Nitriles; D011722:Pyrethrins; D015222:Sodium Channels; D000551:Ambroxol; D013779:Tetrodotoxin; C017690:fenvalerate