Research

Inhibition of citric acid- and capsaicin-induced cough by novel TRPV-1 antagonist, V112220, in guinea-pig

Sum Yee Leung^1,4 , Akio Niimi² , Alison S Williams¹ , Puneeta Nath¹ , F-Xavier Blanc¹ , Q Thai Dinh³ and K Fan Chung¹

¹Thoracic medicine, National Heart & Lung Institute, Imperial College, London, UK

²Department of respiratory medicine, Graduate school of medicine, Kyoto University, Japan

³Department of internal medicine, Charite-Universitatsmedizin Berlin, Berlin, Germany

⁴Department of respiratory medicine, Chang Gung Memorial Hospital, Kaohsiung medical centre, Taiwan

author email corresponding author email

Cough 2007, 3:10doi:10.1186/1745-9974-3-10

Published:	23 December 2007

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.

Conclusion

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.