beta sub(1)- and beta sub(2)-Adrenoceptor antagonist activities of ICI-215001, a putative beta sub(3)-adrenoceptor agonist

• Published in: British journal of pharmacology 1994-01, Vol.112 (1), p.55-58
• Main Authors: Tesfamariam, B, Allen, G T
• Format: Article
• Language: English
• ISSN: 0007-1188

The present study was undertaken to characterize the beta sub(3)-adrenoceptor agonist activity of ICI-215001 and to determine whether it exhibits additional activities on beta sub(1)- and beta sub(2)-adrenoceptors in isolated spontaneously beating atrium, trachea and ileum of guinea-pig. In guinea-pig atrium, isoprenaline, a non-selective beta -adrenoceptor agonist, caused concentration-dependent, positive chronotropic effects that were inhibited by atenolol, a selective beta sub(1)-antagonist. ICI-215001 also competitively antagonized the increase in heart rate caused by isoprenaline. ICI-215001 exhibited low intrinsic activity at increasing the beating rate of atrium and no activity on resting or induced tone of tracheal strips. In strips of guinea-pig trachea, contracted submaximally with carbachol, isoprenaline, caused concentration-dependent relaxations. Both ICI-118551, a selective beta sub(2)-adrenoceptor antagonist, and ICI-215001 competitively inhibited the relaxations caused by isoprenaline. In isolated strips of guinea-pig ileum longitudinal smooth muscle contracted with histamine, isoprenaline and ICI-215001 caused relaxations which were inhibited by alprenolol, a beta -adrenoceptor antagonist with modest affinity for beta sub(3)-adrenoceptors, but were resistant to ICI-118551 and atenolol.