Lack of evidence for beta-2 receptor selectivity: a study of metaproterenol, fenoterol, isoproterenol, and epinephrine in patients with asthma

Abstract

In order to investigate the pharmacodynamic selectivity of a number of beta-receptor agonists currently used in asthma, we compared the pulmonary and extrapulmonary effects of repeated inhalations of epinephrine, fenoterol, isoproterenol, and metaproterenol in 12 patients with asthma in a randomized double-blind crossover study. The drugs were administered from metered-dose inhalers at 15-min intervals for five doses (total dose, 10 puffs of each compound). Measurements of heart rate, blood pressure, total electromechanical systole (as a measure of inotropic response), QTc interval, plasma potassium, and FEV1 were made 5 min after each dose and 30 min after the final dose. Fenoterol and metaproterenol had significantly greater inotropic, electrocardiographic, chronotropic, and hypokalemic effects than did both isoproterenol and epinephrine. There was no difference in the bronchodilating effect of metaproterenol, fenoterol, or isoproterenol although these agents caused a significantly greater increase in FEV1 than did epinephrine. The concept of increasing beta-2 selectivity for metaproterenol and fenoterol compared with isoproterenol are not supported in the clinical setting.