Theobromine inhibits sensory nerve activation and cough

FASEB J. 2005 Feb;19(2):231-3. doi: 10.1096/fj.04-1990fje. Epub 2004 Nov 17.


Cough is a common and protective reflex, but persistent coughing is debilitating and impairs quality of life. Antitussive treatment using opioids is limited by unacceptable side effects, and there is a great need for more effective remedies. The present study demonstrates that theobromine, a methylxanthine derivative present in cocoa, effectively inhibits citric acid-induced cough in guinea-pigs in vivo. Furthermore, in a randomized, double-blind, placebo-controlled study in man, theobromine suppresses capsaicin-induced cough with no adverse effects. We also demonstrate that theobromine directly inhibits capsaicin-induced sensory nerve depolarization of guinea-pig and human vagus nerve suggestive of an inhibitory effect on afferent nerve activation. These data indicate the actions of theobromine appear to be peripherally mediated. We conclude theobromine is a novel and promising treatment, which may form the basis for a new class of antitussive drugs.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Animals
  • Antitussive Agents / pharmacology
  • Antitussive Agents / therapeutic use
  • Capsaicin / adverse effects
  • Citric Acid / adverse effects
  • Codeine / pharmacology
  • Codeine / therapeutic use
  • Cough / chemically induced
  • Cough / prevention & control*
  • Cross-Over Studies
  • Disease Models, Animal
  • Double-Blind Method
  • Female
  • Guinea Pigs
  • Humans
  • In Vitro Techniques
  • Male
  • Neurons, Afferent / drug effects*
  • Theobromine / pharmacology*
  • Theobromine / therapeutic use
  • Vagus Nerve / drug effects


  • Antitussive Agents
  • Citric Acid
  • Theobromine
  • Capsaicin
  • Codeine