Salmeterol (DB00938): A Comprehensive Pharmacological and Clinical Monograph

1.0 Executive Summary

Salmeterol is a small molecule drug classified as a highly potent and selective long-acting β2-adrenergic receptor agonist (LABA). Its clinical significance is rooted in its unique molecular structure, which features a long, lipophilic side chain that confers an extended duration of action of approximately 12 hours. This characteristic has established Salmeterol as a cornerstone of maintenance therapy for persistent asthma and Chronic Obstructive Pulmonary Disease (COPD), where it provides sustained bronchodilation. The primary mechanism of action involves stimulation of β2-receptors in bronchial smooth muscle, leading to an increase in intracellular cyclic AMP (cAMP) and subsequent muscle relaxation.

Despite its pronounced efficacy in controlling symptoms of obstructive lung disease, the clinical profile of Salmeterol is defined by a critical safety consideration. The Salmeterol Multi-center Asthma Research Trial (SMART) identified an increased risk of asthma-related death and life-threatening events when the drug was used as monotherapy. This finding fundamentally reshaped asthma treatment paradigms and led to a stringent boxed warning from the U.S. Food and Drug Administration (FDA). Consequently, the use of Salmeterol for asthma is now mandated to be in combination with an inhaled corticosteroid (ICS), which addresses the underlying inflammation that Salmeterol monotherapy can mask. In contrast, for COPD, where the pathophysiology and risk-benefit calculus differ, Salmeterol may be used as monotherapy or in combination with an ICS.