Effect of procaterol on the isolated airway smooth muscle and the release of anaphylactic chemical mediators from the isolated lung fragments.

The effects of an orally active and selective beta 2-stimulant, procaterol (OPC-2009) on the isolated pulmonary smooth muscle and the release of chemical mediators from the passively sensitized lung fragments were studied and compared with those of isoprenaline (isoproterenol) and salbutamol. Procaterol potently relaxed the isolated guinea pig trachea and lung parenchyma in a concentration-dependent fashion. The drug at a similar range of concentrations antagonized the contraction of the isolated guinea pig trachea and lung parenchyma or human bronchus induced by leukotriene (LT) D4. Salbutamol and isoprenaline also showed similar effects to those of procaterol on the above experiments, but the potencies were consistently weaker than that of procaterol. The release of either histamine or LTs from the passively sensitized human lung fragments was markedly and dose-dependently inhibited by both the 5 min and 15 h treatment with procaterol (10(-10)-10(-7) mol/l) before antigen challenge. Isoprenaline and salbutamol in 5 min treatment experiments showed similar potency as and less potency than procaterol, respectively, on the release of these mediators, but the inhibition potencies of these drugs, particularly isoprenaline, were remarkably reduced by 15 h treatment. From these results, procaterol, besides the existing use as a bronchodilator, is expected to be a potentially prophylactic drug for allergic asthma because of the strong inhibition of the anaphylactic mediator release.