THE PHARMACOLOGY OF SALMETEROL

Salmeterol was developed to provide prolonged bronchodilatation to con trol nocturnal symptoms and improve maintenance therapy in asthmatic p atients. Salmeterol is > 10,000 times more lipophilic than salbutamol and has greater affinity for the beta2-adrenoceptor. Membrane binding is non-competitive and dissociation is slow so that its effects last f or many hours. Despite this, salmeterol does not accumulate in tissues . Its mechanism of action can be explained by binding to a specific ex o-site domain of the beta2-receptor protein to produce continuous stim ulation of the active site of the receptor, which gives salmeterol a p rofile of pharmacological activity unlike that of other beta2-agonists . Due to its potent and prolonged activation of beta2-adrenoceptors in airway smooth muscle cells, endothelial cells, mast cells and epithel ial cells, salmeterol induces prolonged bronchodilatation, reduced vas cular permeability, inhibition of inflammatory mediators, stimulation of ciliary function and modulation of ion and water transport across t he bronchial mucosa.