Tiotropium bromide

Description

Tiotropium bromide is a long-acting inhaled muscarinic antagonist, developed for the once-daily treatment of chronic obstructive pulmonary disease. Tiotropium bromide can be prepared in three steps. The Grignard condensation of 2-thienyl magnesium bromide with oxalic acid dimethyl ester, followed by a transesterlfication with scopine provided the ester which was quaternized with methyl bromide. Tiotropium bromide binds to human recombinant muscarinic receptors M₁-, M₂- and M₃-subtypes with high and similar affinity, comparable to those obtained with ipratropium. Tiotropium bromide is characterized by its novel property of kinetic selectivity : while ipratropium rapidly dissociated from each of the receptor subtypes, tiotropium dissociated rapidly from M₂ receptors (t_1/2=3.6 h) but slowly from MI (t_1/2=14.6 h) and M₃ (t_1/2=34.7 h) receptors. Inhibition of cholinergic bronchospasm by tiotropium bromide was demonstrated in anesthetized guinea pigs, rabbits and dogs. In healthy volunteers, inhalation of tiotropium bromide resulted in an absolute bioavailability of 19.5%, a t,,, value of 5 min. and the terminal half-life value of 5-6 days. There was no evidence of drug accumulation after repeated administration. The extent of biotransfonation was small with a urinary excretion of 74% of unchanged substance after iv. administration. Long term studies in patients with stable COPD have demonstrated that tiotropium bromide gave an effective bronchodilation that was maintained over 24h, significantly improved lung function as measured by FEVI (+ll-12%) and showed progressive reduction in dyspnea. It also reduced exacerbations of COPD patients and improved quality of life. Tiotropium bromide produced greater and more sustained bronchodilation than ipratropium bromide. Tiotropium has been shown to cause superior bronchodilatation and symptomatic improvements when compared to twice daily salmeterol in COPD. Tiotropium bromide was well tolerated and caused few adverse effects. The most common side effect reported was the mechanism-related effect of dry mouth.

The Uses of Tiotropium bromide

Muscarinic receptor antagonist. Bronchodilator

What are the applications of Application

Tiotropium Bromide is an antimuscarinic compound that prevents binding of acetylcholine