ANTIMUSCARINIC EFFECT OF TIQUIZIUM BROMIDE IN-VITRO AND IN-VIVO

Objective: We studied the bronchodilatory effect of tiquizium bromide 2-thienylmethylene)-5-methyl-trans-quinolizidinium bromide; TQZ], an a ntimuscarinic agent, on airway smooth muscle in vitro, and also in pat ients with chronic obstructive pulmonary disease (COPD). Methods: In t he first experiment, canine tracheal smooth muscle was used to measure the pA2 of TQZ in vitro. The selectivity of TQZ for muscarinic recept or subtypes was also examined with a radioligand binding assay. Result s: The pA2 value of TQZ was 8.75. The pK(i) values of TQZ for M1, M2, and M3 were 8.70, 8.94, and 9.11, respectively. In an open pilot exper iment, the effects of TQZ inhalation were studied in seven patients wi th COPD (seven men, mean age 68.5 years). TQZ significantly increased forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1 )) in a dose-dependent manner. The mean maximum increases in FVC and F EV(1) caused by inhaled TQZ (2.0 mg) were 24% and 29%, respectively, a nd they were measured Ih after the drug had been inhaled. The FVC and FEV(1) were still significantly higher than the control values even 8 h after the drug had been inhaled. No adverse effects were observed af ter inhalation of TQZ. Conclusion: These data suggest that TQZ is an e ffective antimuscarinic agent, and that it causes significant bronchod ilation in patients with COPD.