Tiotropium is a long-acting anticholinergic drug. Studies
with cloned human muscarinic receptors show that tiotropium binds
equally well to M1, M2, and M3
receptors. However, it dissociates very slowly from M1 and
M3 receptors compared with ipratropium, and more rapidly
from M2 receptors. Binding studies with
[3H]tiotropium in human lung show that it is
approximately 10-fold more potent than ipratropium. In
vitro, tiotropium has a potent inhibitory effect against
cholinergic nerve-induced contraction of airways. It dissociates
extremely slowly, compared with the dissociation of atropine and
ipratropium. Clinical studies with single doses of inhaled tiotropium
confirm that it is a potent and long-lasting bronchodilator.
Furthermore, it protects against cholinergic bronchoconstriction for
> 24 h. Pharmacokinetic studies show that little of the inhaled drug
is absorbed, thus predicting a high margin of safety.