FORMOTEROL AND SALMETEROL ARE BOTH LONG-ACTING COMPARED TO TERBUTALINE IN THE ISOLATED-PERFUSED AND VENTILATED GUINEA-PIG LUNG

An isolated, perfused and ventilated guinea-pig lung was used to compare the duration of effect of the bronchodilating beta(2)-adrenoceptor agonists formoterol, salmeterol and terbutaline. Lung conductance was measured real time with the aid of a computer. Bronchoconstriction was induced in the preparation every 10 min by bolus injections of acetylcholine into the pulmonary artery. Lung conductance was reduced by about 70% after acetylcholine. The test compounds or the vehicle was administered for 1 min as aerosols generated from solutions: formoterol (10 mu mol/l), salmeterol (100 mu mol/l) and terbutaline (1000 mu mol/l). This treatment inhibited the response to acetylcholine by 50-60% within the first 10 min for all three test compounds. The onset of action appeared to be slower for salmeterol than for formoterol and terbutaline. The inhibitory effect of terbutaline disappeared completely during the next 20 min of continuous perfusion (single pass), while both formoterol and salmeterol displayed a significant inhibitory effect 40 min after their administration. Formoterol, when inhaled at a higher dose (100 mu mol/l), caused a 90% inhibition of the response to acetylcholine. This effect was completely reversed by 0.1 mu mol/l propranolol in the perfusion medium. There were in general no major changes in the basal conductance measured between the acetylcholine provocations.