Pharmacological similarities and differences between β2-agonists

AbstractFormoterol and salmeterol are both long-acting bronchodilators that are effective in the treatment of asthma. However, some differences exist in their pharmacology that are reflected in their clinical profiles. Formoterol has a rapid onset of action, whereas salmeterol causes bronchodilation in a somewhat slower manner. However, both of these drugs are long-acting. After single doses clear effects are maintained for 12 hafter, inhalation, and with high doses effects are observed even at 24 h. Differences between the maximal effects of both drugs are also a consequence of their pharmacological properties. Thus, formoterol has higher intrinsic activity than salmeterol, which means that it is a full agonist, whereas salmeterol is a partial agonist on the β2-receptor. Physicochemical properties of the drugs may explain the differences in onset and duration of action. Adequate water solubility and moderate lipophilicity of formoterol ensures rapid diffusion to the β2-receptor on the smooth muscle and rapid bronchodilating activity. Salmeterol, on the other hand, may diffuse more slowly to the β2-receptor because of its high lipophilicity explaining the slower onset of action. Unlike salbutamol, which is hydrophilic and has a rapid onset and short duration of action, both formoterol and salmeterol possess adequate lipophilic properties to remain in the airway tissues as a depot in close vicinity to the β2-receptor, explaining their long duration of effect. The long duration of salmeterol has also been suggested to depend on an anchored binding within the β2-receptor (I). The pharmacological evidence for a rapid onset of action of formoterol, but long duration of effect, is supported by several clinical studies. The fast onset of bronchodilation and high intrinsic activity of formoterol therefore suggest that it can be used for relief treatment in patients with asthma if they are concomitantly treated with inhaled glucorticoids