TY - JOUR T1 - An assessment of the functional profile of aclidinium in human bronchi and left atria JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p859 AU - Javier Milara AU - Elena Gabarda AU - Amadeu Gavaldà AU - Montserrat Miralpeix AU - Jorge Beleta AU - Esteban Morcillo AU - Julio Cortijo Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p859.abstract N2 - Introduction: Aclidinium bromide is a novel, long-acting muscarinic antagonist, currently in development for the treatment of chronic obstructive pulmonary disease.Aims: To assess the functional profile of aclidinium in isolated human bronchi and left atria, the organs responsible for efficacy and systemic side effects, respectively.Methods: The smooth muscle relaxant effects of aclidinium, tiotropium and ipratropium were measured in isolated human bronchial rings by determining potency, onset (time to 50% inhibition) and offset (time to 50% recovery). The effects of the muscarinic antagonists were assessed in human left-atria strips pre-treated with carbachol 10μM to inhibit electrically-induced contractions via the M2 receptor. Duration of action was defined as the time required to recover 50% of the carbachol effect.Results: Aclidinium had similar potency to tiotropium and ipratropium in human bronchi. Aclidinium onset (4.4±0.7 min) was faster than tiotropium (7.4±1.3 min; p<0.05) and similar to ipratropium (3.3±0.6 min). Aclidinium offset (334±49 min) was longer than ipratropium (76±9 min; p<0.05). Tiotropium did not recover within 10 h. Aclidinium inhibited the bradycardiac effect of carbachol in human left atria, with a shorter half life (110.2 min; 95% confidence interval [CI] 103.0, 117.3) than tiotropium (159.3 min; 95% CI 148.2, 171.7) but longer than ipratropium (16.6 min; 95% CI 16.4, 16.8).Conclusions: Aclidinium has similar potency but faster onset of action than tiotropium in human bronchi. In human left atria, aclidinium had a shorter duration of action than tiotropium at M2 receptors, suggesting a lower potential for cardiovascular side effects. ER -