A comparison between clenbuterol, salbutamol and terbutaline in relation to receptor binding and in vitro relaxation of equine tracheal muscle

Abstract

Beta2-adrenoceptor agonists are used as bronchodilators in both humans and horses. Of these drugs, clenbuterol is the one most frequently used when treating chronic obstructive pulmonary disease in the horse, while salbutamol and terbutaline are used in the treatment of human asthma. Little is known of the properties of the latter two drugs in equine medicine. We have compared salbutamol and terbutaline with clenbuterol in relation to their ability to relax muscle strips from equine tracheal muscle, precontracted with 40 nM carbachol, in tissue chambers. The affinities of these drugs to the beta2-adrenoceptors in homogenates of the same muscle tissue were also examined. These experiments were performed with radioligand binding studies using the very potent beta-adrenoceptor antagonist 125I-cyanopindolol. The three drugs were almost equipotent in relaxing the muscle strips. The EC50-values for salbutamol, terbutaline and clenbuterol were 5.6, 13.8 and 2.1 nM, respectively, and all three drugs relaxed the preparations completely. In the competitive binding study, however, the Kd-value of clenbuterol was much lower (24 nM) than that of salbutamol and terbutaline (1100 nM and 3900 nM, respectively). The amount of receptors bound at the EC50-value of clenbuterol was 8% compared to less than 1% for salbutamol and terbutaline. This indicates a lower intrinsic efficacy of clenbuterol than of the other two drugs. The beta-adrenoceptor density was 45 +/- 14.3 fmol/mg protein (mean +/- SD) and the Kd-value of 125I-cyanopindolol was 11.4 +/- 3.3 pM.