Effects of inhaled thiazinamium chloride on histamine-induced and exercise-induced bronchoconstriction

The protective efficacy of aerosolized thiazinamium chloride (TC) against histamine-induced and exercise-induced bronchoconstriction was evaluated in 15 subjects with stable, mild asthma. Following reproducible bronchoprovocation with these stimuli, each subject underwent randomized, double-blind, crossover pretreatment with single doses of nebulized TC (300, 600, and 900 micrograms), placebo, and an active control drug (metaproterenol or cromolyn), followed by histamine or exercise challenge (two separate protocols). The results indicated that all doses of TC significantly blocked histamine-induced bronchoconstriction as compared with placebo. Overall, aerosolized TC was ineffective in blocking exercise-induced bronchoconstriction, although 900 micrograms TC tended to be more effective than placebo. Thiazinamium (900 micrograms) produced a modest bronchodilator effect. No clinically significant adverse effects related to TC occurred. We conclude that aerosolized TC is effective in attenuating histamine-induced but not exercise-induced bronchoconstriction in the doses studied. Further studies are warranted to evaluate the role of TC in asthma therapy.