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.

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.

• Authors: Sum Yee Leung, Akio Niimi, Alison S Williams, Puneeta Nath, F-Xavier Blanc, Q Thai Dinh, K Fan Chung
• Journal: Cough (London, England) (Cough) Vol. 3 Pg. 10 (Dec 23 2007) ISSN: 1745-9974 [Electronic] England
• PMID: 18154688 (Publication Type: Journal Article)