title: Inhibition of citric acid- and capsaicin-induced cough by novel TRPV-1 antagonist, V112220, in guinea-pig.
abstract: BACKGROUND
  Cough reflex can be induced by the pepper extract capsaicin and by low pH in guinea-pig airways. Transient receptor potential vanniloid-1 (TPRV-1) is expressed in the sensory and afferent nerve fibres in airways.
  
  
  OBJECTIVE
  We hypothesized that a novel pyridazinylpiperazine analog TPRV-1 inhibitor can effectively reduce cough reflex stimulated by citric acid and capsaicin.
  
  
  METHODS
  Guinea pigs were injected with specific TPRV-1 inhibitor, V112220, a pyridazinylpiperazine analog of N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl) tetrahydropyrazine-1(2H)-carbox-amide (BCTC) (3 mg/kg) intra-peritoneally. One hour before cough response assessment. Coughs were recorded using a recorder system that identified cough sound and accompanying expiratory flows, distinct from sneezes. Guinea-pigs exposed to citric acid (0.4 M) and to capsaicin (10-4M) aerosols, in succession separately by 2 hours.
  
  
  RESULTS
  V112220 significantly inhibited the number of coughs induced by citric acid (73 +/- 11%, p < 0.01) and capsaicin (70 +/- 9.4%, p < 0.05) compared to vehicle control.
  
  
  CONCLUSIONS
  A novel pyridazinylpiperazine analog TPRV-1 inhibitor can inhibit the cough reflex, induced by both low pH and capsaicin, suggesting that it could be clinically beneficial in treatment of cough.
authors.affiliation: Thoracic medicine, National Heart & Lung Institute, Imperial College, London, UK. sumyeeleung@hotmail.com
authors.forename: Sum Yee
authors.initials: SY
authors.lastname: Leung
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
authors.forename: Alison S
authors.initials: AS
authors.lastname: Williams
authors.forename: Puneeta
authors.initials: P
authors.lastname: Nath
authors.forename: F-Xavier
authors.initials: FX
authors.lastname: Blanc
authors.forename: Q Thai
authors.initials: QT
authors.lastname: Dinh
authors.forename: K Fan
authors.initials: KF
authors.lastname: Chung