The Use of Functional Antagonism to Determine Whether Beta-adrenoceptor Agonists Must Have a Lower Efficacy Than Isoprenaline to Be Trachea-atria Selective in Vitro in Guinea-pigs

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1977 Jun 1

PMID 18249

Citations 13

Authors

S R ODonnell

J C Wanstall

Affiliations

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Abstract

1 The relative efficacies of three trachea-atria selective beta-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 beta-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 beta-adrenoceptor agonists provided a comparison of their efficacies. 3 On atrial preparations carbachol was used as a functional antagonist of the beta-adrenoceptor agonists and comparison of the maximum responses to the beta-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 Me454 greater than Me506 greater than or equal to isoprenaline=fenoterol. 5. The results indicated that high efficacy in a non-catechol beta-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 effficacies 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.

Citing Articles

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Influence of tracheal contraction on relaxant effects in vitro of theophylline and isoprenaline.

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Relaxation of cat trachea by beta-adrenoceptor agonists can be mediated by both beta1- and beta2-adrenoceptors and potentiated by inhibitors of extraneuronal uptake.

ODonnell S, Wanstall J Br J Pharmacol. 1983; 78(2):417-24.

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Dissociation constants of isoprenaline and orciprenaline and their relative efficacies on guinea-pig isolated atria determined by use of an irreversible beta-adrenoceptor antagonist.

Broadley K, Nicholson C Br J Pharmacol. 1981; 72(4):635-43.

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A study of some propranolol analogues for selective beta-adrenoceptor antagonism using A2 values on isolated trachea and atria from guinea-pig.

ODonnell S, Walduck K, Wanstall J Br J Pharmacol. 1980; 68(4):705-10.

PMID: 6103723 PMC: 2044231. DOI: 10.1111/j.1476-5381.1980.tb10863.x.

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