Effect of Fenspiride on Pulmonary Function in the Rat and Guinea Pig

1. Fenspiride is an anti-inflammatory agent that may have a role in reversible obstructive airways disease. Small, but significant, improvements have been seen in airways function and arterial oxygen tension in patients with mild chronic obstructive pulmonary disease. These changes have been attributed to the anti-inflammatory properties of the drug. However, airways function can be improved by other means, e.g. improved ventilation/perfusion ratio or reduced airways resistance. The possibility that fenspiride may have actions other than anti-inflammatory was investigated in two animal species. 2. In the rat, actions on the pulmonary circulation were investigated in the isolated perfused lung, but fenspiride proved to be a poor pulmonary vasodilator, showing only a small reversal of the raised pulmonary artery pressure induced by hypoxia. 3. Ventilation was measured in the anaesthetized rat using whole-body plethysmography. Fenspiride caused no increase in ventilation or changes in arterial blood gases. However, a profound hypotensive action was observed with high doses. 4. The possibility that a decrease in airways resistance ( R aw ) might occur with fenspiride was investigated in anaesthetized guinea pigs. Capsaicin (30 μmol/l) was used to increase baseline R aw through bronchoconstriction. Fenspiride gave a dose-dependent partial reversal of the raised R aw , and its administration by aerosol proved as efficacious as the intravenous route. In addition, the hypotensive side-effect found with intravenous injection was alleviated by aerosolized fenspiride. 5. An anti-bronchoconstrictor action of fenspiride could be one of the mechanisms involved in improving airways function and P ao 2 , seen in mild chronic obstructive pulmonary disease.