The preclinical pharmacological profile of 6-hydroxy-8-[(1R)-1-hydroxy-2-[[2-(4-methoxyphenyl)-1,1-dimethylethyl]amino]ethyl]-2H-1,4-benzoxazin-3(4H)-one monohydrochloride (olodaterol, previously known as BI 1744 CL), a novel, enantiomeric pure, inhaled human  2 -adrenoceptor (h 2 -AR) agonist, was compared with marketed drugs, such as salmeterol and formoterol. In vitro, olodaterol showed a potent, nearly full agonistic response at the h 2 -AR (EC 50 ϭ 0.1 nM; intrinsic activity ϭ 88% compared with isoprenaline) and a significant selectivity profile (219-and 1622-fold against the h 1 -and h 3 -ARs, respectively). Likewise, olodaterol was able to potently reverse contraction induced by different stimuli in isolated human bronchi. In vivo, antagonistic effects of single doses of olodaterol and formoterol were measured against acetylcholine challenges in anesthetized guinea pigs and dogs for up to 24 h by using the Respimat Soft Mist inhaler. Heart rate and metabolic parameters (serum potassium, lactate, and glucose) were monitored to evaluate systemic pharmacodynamic effects in the dog model. In both models, olodaterol provided bronchoprotection over 24 h. Formoterol applied at an equally effective dose did not retain efficacy over 24 h. In both models olodaterol showed a rapid onset of action comparable with formoterol. Taken together, the preclinical behavior of olodaterol suggests that this novel  2 -AR agonist has the profile for once-daily dosing in humans concomitant with a fast onset of action and a favorable systemic pharmacodynamic profile.Asthma and chronic obstructive pulmonary disease (COPD) are conditions characterized by airway obstruction, which is variable and reversible in asthma but is progressive in COPD (Guerra, 2009). Both diseases are very common, and their incidence is increasing globally, placing a growing burden on patients and health services in industrialized and developing countries (Pauwels and Rabe, 2004;Braman, 2006).  2 -Adrenoceptor ( 2 -AR) agonists are among the most potent and rapidly acting bronchodilators currently available for clinical use. In asthma, rapid-acting inhaled  2 -AR agonists are the therapy of choice as a reliever therapy for episodes of dyspnea and the pretreatment of exercise-induced bronchoconstriction (Bateman et al., 2008). In asthma patients with persistent symptoms long-acting -agonists (LABAs), such as salmeterol and formoterol, are administered as an add-on controller therapy when the first-line treatment of medium dose-inhaled corticosteroids alone fails to achieve control of asthma (Bateman et al., 2008). Recently, formoterol has gained some recognition as an as needed controller therapy because of its fast onset of action. In addition, inhaled  2 -AR agonists provide major therapeutic benefits in the treatment of COPD, such as reduction in symptoms and exacerbations, increases in exercise capacity, and improvements of health-related quality of life (Gold, 2009). 2 -AR agonists exert a bronchodilatory effect through activation of ...
