A 35-year-old woman with COPD is prescribed inhaled tiotropium. Compared to ipratropium, tiotropium has a longer duration of action and greater clinical efficacy because of its kinetic selectivity for which muscarinic receptor subtype?

• A Non-selective muscarinic antagonism with longer half-life
• B M2 receptor with rapid dissociation kinetics
• C M1 receptor with irreversible binding
• D M3 receptor with slow dissociation kinetics ✓

Explanation

Tiotropium dissociates slowly from M3 muscarinic receptors on airway smooth muscle, producing bronchodilation lasting over 24 hours. It dissociates rapidly from M2 receptors, which are presynaptic autoreceptors that inhibit acetylcholine release, so its net effect is favorable. This kinetic M3 selectivity explains its once-daily dosing and superiority over ipratropium.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

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