Characterization of the adrenergic activity of carbuterol (SK&F 40383-A)

Abstract

Carbuterol is a β-adrenergic bronchodilator with selectivity for bronchial smooth muscle relative to cardiac and vascular tissues of several species including man. The present studies were undertaken to further characterize its adrenergic profile. In vitro studies demonstrated that carbuterol was a direct acting β-adrenergic agonist, not dependent on endogenous catecholamine release, and was devoid of α-adrenergic agonist activity. The activity of the racemate was shown to reside primarily in the l-enantiomer. Carbuterol inhibited immunologically induced release of histamine and slow reacting substance of anaphylaxis from passively sensitized fragmented Rhesus monkey lung and also inhibited passive cutaneous anaphylaxis in rats. The relatively weak stimulant activity of carbuterol on β 1 receptors mediating both rate and force of contraction was confirmed in anesthetized open-chest dogs. In the anesthetized cat, carbuterol was significantly less potent than isoproterenol in decreasing diastolic blood pressure, increasing heart rate, and decreasing the tension and degree of fusionof incomplete tetanic contraction of the soleus muscle.