Novel antitussive effect of suplatast tosilate in guinea pigs

Pharmacology. 2015;95(1-2):36-41. doi: 10.1159/000369977. Epub 2015 Jan 13.

Abstract

We studied the antitussive effects of suplatast, a Th2 cytokine inhibitor, and compared them with the effects of codeine using an experimental cough model in guinea pigs. Suplatast and codeine dose-dependently inhibited cough caused by mechanical stimulation of the larynx, but they did not inhibit cough caused by mechanical stimulation of the bifurcation of the trachea. In guinea pigs with bronchitis, suplatast had an antitussive effect on cough caused by stimulation of the larynx, whereas codeine did not inhibit such cough. In SO2-exposed guinea pigs, suplatast tended to inhibit cough caused by mechanical stimulation of the tracheal bifurcation. Further, suplatast inhibited citric acid-induced cough augmented by pretreatment with an angiotensin-converting enzyme inhibitor, whereas codeine did not inhibit such cough. Suplatast also inhibited bradykinin-induced discharges of airway vagal afferent nerves and significantly inhibited 4-aminopyridine-induced discharges of airway vagal afferent nerves. These findings indicate that the antitussive effects of suplatast are mediated by a novel mechanism involving the peripheral nervous system.

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Animals
  • Antitussive Agents / pharmacology
  • Antitussive Agents / therapeutic use*
  • Arylsulfonates / pharmacology
  • Arylsulfonates / therapeutic use*
  • Bradykinin / pharmacology
  • Bronchitis / drug therapy*
  • Bronchitis / physiopathology
  • Cough / drug therapy*
  • Cough / physiopathology
  • Guinea Pigs
  • Male
  • Potassium Channel Blockers / pharmacology
  • Respiratory System / innervation
  • Sulfonium Compounds / pharmacology
  • Sulfonium Compounds / therapeutic use*
  • Vagus Nerve / drug effects
  • Vagus Nerve / physiology

Substances

  • Antitussive Agents
  • Arylsulfonates
  • Potassium Channel Blockers
  • Sulfonium Compounds
  • 4-Aminopyridine
  • suplatast tosilate
  • Bradykinin