Table 1.

Preclinical studies comparing the pharmacological profile of glycopyrrolate with other LAMAs and ipratropium

Study	Characteristic	Glycopyrrolate	Aclidinium	Tiotropium	Ipratropium
In vitro calcium assay13	Equilibrium binding constant, mean ± SE:		–		–
	M2	8.70±0.04		10.05±0.03
	M3	9.59±0.05		10.37±0.04
	Drug binding t½ (minutes) at M3 vs M2 receptors (kinetic selectivity ratio)	11.4 vs 1.07 (10.7)	–	46.2 vs 10.8 (4.3)	–
In vitro study of recombinant human receptors16	Muscarinic receptor-binding affinity (Ki, nM), mean ± SE:
	M2	1.77±0.06	0.14±0.04	0.13±0.04	1.12±0.13
	M3	0.52±0.04	0.14±0.02	0.19±0.04	1.24±0.08
Ex vivo binding in rat lungs18	Binding to muscarinic receptors in lung	Binding lasted 24 hours	–	Binding lasted 24 hours	Binding observed at 2 hours, but not at 12 hours
In vitro study of recombinant human receptors16	M3 vs M2 receptors, dissociation t½ in hours (kinetic selectivity ratio)	8.1 vs 1.1 (7.3)	29.2 vs 4.7 (6.2)	62.2 vs 15.1 (4.1)	0.5 vs 0.1 (5.9)
In vivo study in guinea pigs16	Onset of action (hours) postadministration	2	2	4	2
Ex vivo study in human airways19	Onset of action of 1 µM dose, minutes ± SEM	3.4a±0.4	6.4±0.5	8.4±1.1	–
In vitro study in guinea pig trachea16	Duration of action (t½ offset of electrically stimulated contractions) at M3 receptors	>8 hours	>8 hours	>8 hours	42 minutes
In vivo study in guinea pigs16	Duration of bronchodilator action, in hours (t½ offset of maximal inhibitory effect)	13	29	64	8
In vivo rat salivation study16	ED50 (µg/kg) for inhibition of salivation	0.74	38	0.88	–
In vitro human plasma study16	Hydrolysis t½ in plasma (hours)	6	0.04	1.6	33

Notes:

^aP<0.05 vs both aclidinium and tiotropium at equal concentrations. “–” indicates data not available.

Abbreviations: ED₅₀, dose required to inhibit salivation in 50% of rats; K_i, antagonist dissociation constant; LAMAs, long-acting muscarinic antagonists; SE, standard error; SEM, standard error of the mean; t_½, half-life.