The pharmacological properties of tiotropium.

Tiotropium is a long-acting anticholinergic drug. Studies with cloned human muscarinic receptors show that tiotropium binds equally well to M(1), M(2), and M(3) receptors. However, it dissociates very slowly from M(1) and M(3) receptors compared with ipratropium, and more rapidly from M(2) receptors. Binding studies with [(3)H]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.

[1]  P. Barnes,et al.  Muscarinic receptor subtypes in airways. , 1993, The European respiratory journal.

[2]  T. Witek,et al.  Tiotropium (Spiriva): mechanistical considerations and clinical profile in obstructive lung disease. , 1999, Life sciences.

[3]  F. Maesen,et al.  Tiotropium bromide, a new long-acting antimuscarinic bronchodilator: a pharmacodynamic study in patients with chronic obstructive pulmonary disease (COPD). Dutch Study Group. , 1995, The European respiratory journal.

[4]  P. Barnes,et al.  Autoradiographic visualization of muscarinic receptor subtypes in human and guinea pig lung. , 1990, The American review of respiratory disease.

[5]  M. Yacoub,et al.  Modulation of cholinergic neural bronchoconstriction by endogenous nitric oxide and vasoactive intestinal peptide in human airways in vitro. , 1993, The Journal of clinical investigation.

[6]  P. Barnes,et al.  Tiotropium bromide (Ba 679 BR), a novel long-acting muscarinic antagonist for the treatment of obstructive airways disease. , 1995, Life sciences.

[7]  P. Barnes,et al.  Characterization of [3H]Ba 679 BR, a slowly dissociating muscarinic antagonist, in human lung: radioligand binding and autoradiographic mapping. , 1994, Molecular pharmacology.

[8]  M. Yacoub,et al.  Evidence for prejunctional muscarinic autoreceptors in human and guinea pig trachea. , 1995, American journal of respiratory and critical care medicine.

[9]  P. Barnes,et al.  Duration of protection by oxitropium bromide against cholinergic challenge. , 1987, European journal of respiratory diseases.

[10]  H. Dean,et al.  Parasympathetic nervous system in nocturnal asthma , 1988, British medical journal.

[11]  B. Disse,et al.  Ba 679 BR, a novel long-acting anticholinergic bronchodilator. , 1993, Life sciences.

[12]  M. Yacoub,et al.  Effect of Ba 679 BR, a novel long-acting anticholinergic agent, on cholinergic neurotransmission in guinea pig and human airways. , 1994, American journal of respiratory and critical care medicine.

[13]  P. Barnes,et al.  Prolonged effect of tiotropium bromide on methacholine-induced bronchoconstriction in asthma. , 1996, American journal of respiratory and critical care medicine.