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.