Profile of the effect of aclidinium bromide compared to glycopyrronium bromide

Introduction

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway obstruction and chronic inflammation in the airways and lungs. The primary parasympathetic neurotransmitter in the airways is acetylcholine, which regulates smooth muscle tone and mucus secretion through muscarinic receptors (the airways contain M₁−M₃ receptors). Anticholinergics, specifically muscarinic receptor antagonists, are recommended as first-line bronchodilator treatment for patients with COPD.

Main Findings from the Study

A study by Spanish authors examined the profiles of 2 long-acting muscarinic receptor antagonists (LAMA), aclidinium bromide and glycopyrronium bromide, under in vitro and in vivo conditions, using tiotropium bromide (LAMA) and ipratropium bromide (SAMA – short-acting antimuscarinic agent) as comparators:

• All 4 antagonists had high affinity for all 5 muscarinic receptor subtypes (M₁−M₅), with aclidinium and tiotropium having comparable affinities, which were higher than those of glycopyrronium and ipratropium.
• In vitro, tiotropium, aclidinium, and glycopyrronium remained bound to native M₃ receptors longer (> 8 hours) than ipratropium (42 minutes); tiotropium remained bound the longest, and aclidinium dissociated more slowly than glycopyrronium.
• All substances dissociated more quickly from M₂ receptors than from M₃ receptors.
• In in vivo acetylcholine-induced bronchoconstriction, all substances were comparably effective.
• Aclidinium, glycopyrronium, and ipratropium had a faster onset of bronchodilator activity than tiotropium.
• The duration of bronchodilator effect decreased in the order: tiotropium, aclidinium, glycopyrronium, ipratropium.
• Aclidinium underwent the fastest plasma hydrolysis, with a half-life 150 times shorter than that of glycopyrronium and 40 times shorter than that of tiotropium.
• In in vivo studies, aclidinium less suppressed salivation compared to glycopyrronium and tiotropium.

Conclusion

The results suggest that while both aclidinium and glycopyrronium are effective muscarinic receptor antagonists with similar selectivity for M₃ receptors over M₂ receptors, aclidinium dissociates more slowly from M₃ receptors, resulting in a longer in vivo bronchodilator effect compared to glycopyrronium. At the same time, it undergoes rapid plasma hydrolysis, reducing systemic drug burden and the risk of systemic anticholinergic adverse effects.

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Source: Gavaldà A., Ramos I., Carcasona C. et al. The in vitro and in vivo profile of aclidinium bromide in comparison with glycopyrronium bromide. Pulm Pharmacol Ther 2014; 28 (2): 114−121, doi: 10.1016/j.pupt.2014.05.005.