Possible involvement of tetrodotoxin-resistant sodium channels in cough reflex

• Published in: European journal of pharmacology Vol. 652; no. 1; pp. 117 - 120
• Main Authors: Kamei, Junzo, Nakanishi, Yuki, Ishikawa, Yoko, Hayashi, Shun-suke, Asato, Megumi, Ohsawa, Masahiro
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10.02.2011; Elsevier
• Subjects: Ambroxol; Ambroxol - pharmacology; Ambroxol - therapeutic use; Animals; Antitussive; Antitussive Agents - pharmacology; Antitussive Agents - therapeutic use; Biological and medical sciences; breathing; C-fibers; citric acid; cough; Cough - chemically induced; Cough - drug therapy; Cough reflex; dimethyl sulfoxide; Dose-Response Relationship, Drug; fenvalerate; Male; Medical sciences; Mice; Mice, Inbred ICR; Nerve Fibers, Unmyelinated - drug effects; Nerve Fibers, Unmyelinated - metabolism; Nitriles; pharmacology; Pneumology; Pyrethrins; Respiratory system : syndromes and miscellaneous diseases; sodium channels; Sodium Channels - metabolism; tetrodotoxin; Tetrodotoxin - pharmacology; Tetrodotoxin - therapeutic use; Tetrodotoxin-resistant sodium channels; Cough reflex; Tetrodotoxin-resistant sodium channels; C-fibers; Ambroxol; Antitussive; Reflex; Antitussive agent; Ionic channel; Expectorant; Cough; Nerve fiber C; Mucolytic; Sodium
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2010.11.019

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 3 μg/ml, for 5 min produced coughs in a concentration-dependent manner. Pretreatment with tetrodotoxin, at a dose of 1 μg/kg, s.c., slightly but significantly reduced the number of fenvalerate (3 μg/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 1 μg/kg, s.c., almost completely reduced the number of citric acid (0.25 M)-induced coughs to the level in vehicle (saline) alone inhaled mice. Pretreatment with ambroxol, at doses of 10, 30, 100 and 300 mg/kg, p.o., dose-dependently and significantly reduced the number of fenvalerate (3 μg/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.