Effects of antitussive drugs on cough in <i>Ttll1</i>^−/− mice.

(A, B, D, F, H) Graphs displaying the pre- and post-treatment number of coughs. (C) Graph displaying the dose–response relationship of the increased number of coughs in Ttll1−/− mice. (E, G) Graph displaying the number of coughs evoked by inhaled capsaicin in wild-type (WT) mice treated with control and capsazepine (CPZ) or HC-030031. (A) Codeine phosphate (10 mg/kg) or saline was administered by gavage. Codeine phosphate significantly decreased cough in the Ttll1−/− mice. (B) The Ttll1−/− mice were nebulized with salbutamol (5 mg/ml) or phosphate-buffered saline (PBS). Salbutamol did not decrease cough in the Ttll1−/− mice. (C) Moguisteine (3, 10, and 30 mg/kg) or control [0.5% dimethylsulfoxide (DMSO)] was intraperitoneally administered. Administration of 10 and 30 mg/kg moguisteine significantly inhibited cough in the Ttll1−/− mice. (D) The Ttll1−/− mice were nebulized with CPZ (300 μM) or control (10% DMSO). CPZ did not decrease cough in the Ttll1−/− mice. (E) After treatment with nebulized CPZ (300 μM) or control (10% DMSO), the WT mice were nebulized with capsaicin to evoke cough. Nebulization with 300 μM CPZ was sufficient to inhibit cough evoked by capsaicin in the WT mice. (F) Vehicle (0.5% methyl cellulose in sterile saline) or HC-030031 (300 mg/kg) was administered intraperitoneally to the Ttll1−/− mice. HC-030031 did not decrease cough in the Ttll1−/− mice. (G) After administration of HC-030031 (300 mg/kg) or vehicle, the WT mice were nebulized with acrolein (10 mM) to evoke cough. Administration of HC-030031 was sufficient to inhibit cough evoked by acrolein in the WT mice. (H) Lidocaine (4%) or saline was administered to each nostril. Lidocaine decreased cough in the Ttll1−/− mice [bars indicate median values; n = 5–10 mice in each group; *P < 0.05, number of coughs compared between pre- and post-treatment (in A−D, F, H) or between control and treated groups (in E and G) using Wilcoxon signed-rank test; †P < 0.05, increased number (post-treatment–pretreatment) compared with that in the control group using Mann–Whitney U-test; NS = not significant].