In vitro potency and duration of action of CHF5407 as compared with tiotropium, ipratropium, and glycopyrrolate in blocking muscarinic M3 receptor-mediated bronchoconstriction in human and guinea pig airways or M2 receptor-mediated inhibition of electrically induced twitch contractions in guinea pig left atrium
All data are mean ± S.E.M. of at least four observations.
| Compound | Guinea Pig Trachea (Carbachol-Contracted) | Guinea Pig Trachea (EFS-Stimulated | Human Bronchus | Guinea Pig Left Atrium | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| pIC50 | t½ | % Recovery (at 4.5 h) | pIC50 | t½ | % Recovery (at 4 h) | pIC50 | t½ | % Recovery (at 6 h) | pIC50 | t½ | % Recovery (at 4.5 h) | |
| h | h | h | h | |||||||||
| CHF5407 | 9.0 ± 0.04 | >4 | 11 ± 5 | 9.1 ± 0.25 | >4 | 0 | 9.6 ± 0.01 | >6 | 11 ± 9 | 8.2 ± 0.2 | 1.0 ± 0.1 | 73 ± 3 |
| Tiotropium | 9.1 ± 0.001 | >4 | 10 ± 3 | 9.3 ± 0.09 | >4 | 0 | 9.5 ± 0.04 | >6 | 25 ± 2 | 8.7 ± 0.1 | 3.3a ± 0.2 | 58 ± 4 |
| Ipratropium | 8.6 ± 0.02 | 0.5 ± 0.1 | 70 ± 7 | 9.2 ± 0.24 | 0.25 ± 0.1 | 75 ± 8 | 9.5 ± 0.04 | 3.0 ± 0.2 | 110 ± 10 | NT | NT | NT |
| Glycopyrrolate | 9.0 ± 0.07 | 4.0 ± 0.5 | 50 ± 8 | NT | NT | NT | 10.4 ± 0.02 | 3.7 ± 0.2 | 101 ± 10 | NT | NT | NT |
pIC50 represents the log molar concentration of the test antagonist producing a 50% reversal of carbachol or electrical-induced effect. t1/2 (offset) is the time taken for response to carbachol or electrical field stimulation to return to 50% recovery after washout of the test antagonist. % Recovery indicates percentage response to carbachol or electrical field stimulation obtained 4 or 6 h after the washout of the test antagonist. Data for glycopyrrolate and part of data for ipratropium are from Villetti et al., 2006. NT, not tested.
↵a Significantly different from t1/2 of CHF5407; P < 0.05.