Umeclidinium bromide 是mAChR拮抗剂，作用于克隆的人 M1-M5 mAChRs，Ki为 0.05 到 0.16 nM。

Umeclidinium bromide is a novel mAChR antagonist.

In human embryonic kidney 293 cells, Umeclidinium bromide (GSK573719A) inhibits the human ether-a-go-go-related gene channel tail current in a concentration-dependent manner (IC50=9.4 μM).

When Umeclidinium bromide (GSK573719A) is given once daily to mice for 5 consecutive days (0.025 μg intranasally), the level of inhibition on the fifth day is modestly increased above that obtained after a single administration to the same mice (60 versus 35%, respectively). After the fifth day of dosing, the mice are rested for 5 additional days, allowing bronchomotor tone to return to baseline levels. On the sixth day, the mice receive one last dose of antagonist and are once again challenged with Mch. The level of inhibition is essentially the same as that found on the first day of testing, indicating that tolerance is not evident with repeated intranasal delivery of Umeclidinium bromide. On the contrary, when Umeclidinium bromide is given orally (2.0 mg/kg) to mice at a dose 100 times the ED50 value (intranasal), there is no observable protection against an Mch challenge.

Mice:Age-matched male BALB/c mice (23-25 gm) are pretreated intranasally (50 μL per mouse) with vehicle (0.9% saline) or Umeclidinium bromide at intervals (0.25-48 hours) prior to methacholine challenge, and placed into individual plethysmograph chambers. Fresh air is supplied by bias flow pumps to the chambers. After baseline respiratory [enhanced pause (Penh)] values are collected, the mice received methacholine (30 mg/mL or EC80) by aerosol delivery (flow=1.6 mL/min×2 minutes). An average Penh is then calculated for 5 minutes. Penh=[(expiratory time/relaxation time)?1]×(peak expiratory flow/peak inspiratory flow), and relaxation time is the amount of time required for 70% of the tidal volume to expire. In some cases, animals are treated on multiple, consecutive days as described in the figure legends. The data are expressed as the mean±S.E.M. percent inhibition of Penh or (mean Penh value of vehicle treated group-Penh for each drug-treated animal) divided by (mean Penh value of vehicle treated group)×100%. Data are analyzed using commercially available software.

869113-09-7

C29H34BrNO2

508.5

芜地溴铵;GSK573719A;Umeclidinium bromide

DMSO:34 mg/mL (66.86 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years