Ambroxol Improves the Broncho-spasmolytic Activity of Clenbuterol in the Guinea-Pig

Abstract

Abstract The effects of ambroxol on the spasmolytic action of clenbuterol were investigated on acetylcholine-induced bronchospasm in guinea-pigs. Ambroxol (50 mg kg−1 day−1) or vehicle was administered orally for 14 days. Approximately 45 min after the final dose on day 14, the animals were anaesthetized and the spasmolytic effects of clenbuterol (3, 6 or 12 μg kg−1 injected intravenously) were determined by use of acetylcholine (40 μg kg−1, i.v.)-induced bronchoconstriction. For both vehicle- and ambroxol-treated animals, a positive linear relationship was observed between the log-dose of clenbuterol and the percent inhibition of bronchospasm. The calculated ED25 of clenbuterol (i.e. the dose producing 25% inhibition of the acetylcholine-induced bronchospasm) was 3.98 μg kg−1 (3.29 to 4.82 μg kg−1, 95% confidence interval) in the presence of ambroxol and 5.81 μg kg−1 (4.98 to 6.79 μg kg−1) in the absence of ambroxol. The linear regressions with or without ambroxol differed from each other (P < 0001) but ran parallel (covariance analysis), enabling us to calculate a relative potency, the value of which was 1.46 (1.16 to 1.84). These results demonstrate that the spasmolytic activity of clenbuterol is significantly improved in animals pretreated with ambroxol.