From the Guidelines
Tiotropium acts on M2- and M3-muscarinic receptors to dilate airways. According to the study published in Chest in 2015 1, tiotropium inhibits the release of acetylcholine at the receptor level by binding to these receptors, resulting in bronchodilation. The binding of tiotropium to M2- and M3-muscarinic receptors improves outcomes, including quality of life, increased exercise capacity, and a reduction in exacerbations.
Key Points
- Tiotropium is an inhaled long-acting muscarinic antagonist used in the treatment of COPD.
- The mechanism of action of tiotropium involves binding to M2- and M3-muscarinic receptors, which line the airway.
- This binding inhibits the release of acetylcholine, resulting in bronchodilation and improved outcomes.
- The safety profile of tiotropium has been reviewed in several analyses, demonstrating an acceptable safety profile 1.
Muscarinic Receptors
The M2- and M3-muscarinic receptors are the primary targets of tiotropium, with the M3 receptors being particularly important as they are found on airway smooth muscle and directly mediate bronchoconstriction when stimulated. By blocking these muscarinic receptors, tiotropium reduces airway smooth muscle tone, increases airway diameter, and improves airflow in conditions like 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
The muscarinic receptor that tiotropium acts on to dilate airway is the M3-receptor. Tiotropium has similar affinity to the subtypes of muscarinic receptors, M1 to M5, but it exhibits pharmacological effects through inhibition of M3-receptors at the smooth muscle leading to bronchodilation 2.
From the Research
Muscarinic Receptors and Tiotropium
Tiotropium acts on muscarinic receptors to dilate airways. The human airways have five subtypes of muscarinic cholinergic receptors: M1, M2, M3, M4, and M5.
- M1 and M3 mediate bronchoconstriction and stimulation of mucus secretion
- M2 controls the release of acetylcholine from M1 and M3 receptors through a negative-feedback mechanism 3
Tiotropium's Mechanism of Action
Tiotropium dissociates more slowly from M1 and M3 than from M2 receptors, which contributes to its long duration of action 3.
- Tiotropium has a high affinity to M3 receptors 4, 5
- Tiotropium binds not only to its main binding site on the M3 muscarinic receptor but also to an allosteric site, which contributes to its bronchoprotective effects 6
Receptor Subtypes Involved
The primary muscarinic receptor subtypes involved in tiotropium's action are: