title: Theobromine inhibits sensory nerve activation and cough.
abstract: 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.
authors.affiliation: Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Omar S
authors.initials: OS
authors.lastname: Usmani
authors.forename: Maria G
authors.initials: MG
authors.lastname: Belvisi
authors.forename: Hema J
authors.initials: HJ
authors.lastname: Patel
authors.forename: Natascia
authors.initials: N
authors.lastname: Crispino
authors.forename: Mark A
authors.initials: MA
authors.lastname: Birrell
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
authors.forename: Dezso
authors.initials: D
authors.lastname: Korbonits
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
mesh_terms: D000328:Adult; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology / Q000627:therapeutic use; D002211:Capsaicin / Q000009:adverse effects; D019343:Citric Acid / Q000009:adverse effects; D003061:Codeine / Q000494:pharmacology / Q000627:therapeutic use; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control*; D018592:Cross-Over Studies; D004195:Disease Models, Animal; D004311:Double-Blind Method; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D013805:Theobromine / Q000494:pharmacology* / Q000627:therapeutic use; D014630:Vagus Nerve / Q000187:drug effects
chemical_list: D000996:Antitussive Agents; D019343:Citric Acid; D013805:Theobromine; D002211:Capsaicin; D003061:Codeine