From the Guidelines
Tiotropium acts on M2- and M3-muscarinic receptors, which line the airway, inhibiting the release of acetylcholine and resulting in bronchodilation. According to the study published in Chest in 2015 1, tiotropium is an inhaled long-acting muscarinic antagonist used in the treatment of COPD, and its mechanism of action involves binding to these specific muscarinic receptors. The resulting bronchodilation has improved outcomes, including quality of life, increased exercise capacity, and a reduction in exacerbations. Some key points about tiotropium's mechanism of action include:
- Inhibition of acetylcholine release at the receptor level
- Binding to M2- and M3-muscarinic receptors
- Resulting bronchodilation and improved outcomes The study 1 highlights the importance of tiotropium's selective action on these muscarinic receptors, particularly in the context of COPD treatment. By blocking M2- and M3-muscarinic receptors, tiotropium prevents acetylcholine from binding to these receptors, which inhibits bronchoconstriction and promotes bronchodilation. This makes tiotropium effective as a long-acting anticholinergic bronchodilator for treating COPD.
From the FDA Drug Label
Tiotropium is a long-acting, muscarinic antagonist which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors, M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3-receptors at the smooth muscle leading to bronchodilation
- Muscarinic receptors affected by tiotropium: M1 to M5, with a specific effect on M3-receptors in the airways.
- Tiotropium's action on these receptors leads to bronchodilation. 2
From the Research
Muscarinic Receptors and Tiotropium
Tiotropium acts on several muscarinic receptors, including:
- M1 receptors: Tiotropium binds to M1 receptors and dissociates very slowly from them 3, 4
- M2 receptors: Tiotropium binds to M2 receptors, but dissociates more rapidly from them compared to M1 and M3 receptors 3, 4
- M3 receptors: Tiotropium has a high affinity for M3 receptors and dissociates very slowly from them 3, 5, 4, 6, 7
Binding Characteristics
The binding characteristics of tiotropium to muscarinic receptors are:
- High potency: Tiotropium is approximately 10-fold more potent than ipratropium 4
- Slow dissociation: Tiotropium dissociates very slowly from M1 and M3 receptors, which contributes to its long duration of action 3, 4, 7
- Kinetic selectivity: Tiotropium has kinetic selectivity for M3 receptors over M2 receptors, which may contribute to its clinical effects 3, 7
Clinical Implications
The clinical implications of tiotropium's binding characteristics are:
- Long-lasting bronchodilation: Tiotropium's slow dissociation from muscarinic receptors contributes to its long-lasting bronchodilatory effects 3, 4
- Protection against cholinergic bronchoconstriction: Tiotropium's high affinity for M3 receptors and slow dissociation contribute to its ability to protect against cholinergic bronchoconstriction 3, 5, 6