Antimuscarinic effect of tiquizium bromide in vitro and in vivo.
OBJECTIVE
We studied the bronchodilatory effect of tiquizium bromide [3-(di-2-thienylmethylene)-5 methyl-trans-quinolizidinium bromide; TQZ], an antimuscarinic agent, on airway smooth muscle in vitro, and also in patients with chronic obstructive pulmonary disease (COPD).


METHODS
In the first experiment, canine tracheal smooth muscle was used to measure the pA2 of TQZ in vitro. The selectivity of TQZ in vitro. The selectivity of TQZ for muscarinic receptor subtypes was also examined with a radioligand binding assay.


RESULTS
The pA2 value of TQZ was 8.75. The pKi values of TQZ for M1, M2, and M3 were 8.70, 8.94, and 9.11, respectively. In an open pilot experiment, the effects of TQz inhalation were studied in seven patients with COPD (seven men, mean age 68.5 years). TQZ significantly increased forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) in a dose-dependent manner. The mean maximum increases in FVC and FEV1 caused by inhaled TQZ (2.0 mg) were 24% and 29%, respectively, and they were measured 1 h after the drug had been inhaled. The FVC and FEV1 were still significantly higher than the control values even 8 h after the drug had been inhaled. No adverse effects were observed after inhalation of TQZ.


CONCLUSIONS
These data suggest that TQZ is an effective antimuscarinic agent, and that it causes significant bronchodilation in patients with COPD.
Shioya
T
T
Second Department of Internal Medicine, Akita University School of Medicine, Japan.
Kagaya
M
M
Sano
M
M
Itaba
M
M
Shindo
T
T
Miura
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009241:Ipratropium / Q000494:pharmacology; D008173:Lung Diseases, Obstructive / Q000503:physiopathology*; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D011807:Quinolizines / Q000008:administration & dosage / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011869:Radioligand Assay; D012602:Scopolamine Derivatives / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism; D014797:Vital Capacity / Q000187:drug effects
D001286:Atropine Derivatives; D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D011807:Quinolizines; D012602:Scopolamine Derivatives; D011813:Quinuclidinyl Benzilate; C030950:thiaton; D001285:Atropine; C017590:oxitropium; D009241:Ipratropium; C039778:flutropium bromide; D000109:Acetylcholine