THE USE OF FUNCTIONAL ANTAGONISM TO DETERMINE WHETHER β‐ADRENOCEPTOR AGONISTS MUST HAVE A LOWER EFFICACY THAN ISOPRENALINE TO BE TRACHEA‐ATRIA SELECTIVE in vitro IN GUINEA‐PIGS

Abstract

1 The relative efficacies of three trachea-atria selective β-adrenoceptor agonists, fenoterol, Me 506 and Me 454, compared to isoprenaline, were determined on both trachea and atria of guinea-pigs. 2 On tracheal preparations the β-adrenoceptor agonists were used as functional antagonists of carbachol and a comparison of the maximum shifts in the carbachol concentration-response line produced by each of the β-adrenoceptor agonists provided a comparison of their efficacies. 3 On atrial preparations carbachol was used as a functional antagonist of the β-adrenoceptor agonists and comparison of the maximum responses to the β-adrenoceptor agonists in the presence of carbachol provided a comparison of their efficacies. 4 On trachea and atria the order of efficacy of the compounds was Me 454 > Me 506 ≥ isoprenaline = fenoterol. 5 The results indicated that high efficacy in a non-catechol β-adrenoceptor agonist is possible provided there is a favourable N-substituent group. 6 Since Me 454, Me 506 and fenoterol, which are trachea-atria selective, have efficacies equal to or greater than that of isoprenaline, which is non-selective, it is concluded that low efficacy in a compound is not essential for it to show trachea-atria selectivity in vitro in guinea-pigs.