Evidence that ICI 118, 551 is a potent, highly beta2-selective adrenoceptor antagonist and can be used to characterize beta-adrenoceptor populations in tissues

Abstract

pA values for a new ß-adrenoceptor antagonist, ICI 118, 551 (erythro-DL-1(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-o1), have been obtained on intrinsic tone tracheal chain preparations and on spontaneously beating atrial preparations from guinea-pigs. Two different agonists, fenoterol (ß-selective) and noradrenaline (ß-selective) were used. The slopes of the Schild plots were not significantly different from 1.0. The antagonist was very potent (pA on trachea, fenoterol as agonist, was 8.69) and also highly ß-selective (pA on atria, noradrenaline as agonist, was only 6.96). On guinea-pig trachea (which contains ß- and ß-adrenoceptors) the potency was 44 times higher when fenoterol was the agonist than when noradrenaline was the agonist. On guinea-pig atria (which contains only ß-adrenoceptors) the pA value was the same whichever agonist was used. Thus ICI 118, 551 has been shown to be potent and the most ß-selective antagonist so far studied in our laboratory. In experiments carried out with selective agonists ICI 118, 551 distinguished clearly between tissues with a mixed ß-adrenoceptor population (different pA values) and those with a homogeneous population (single pA value). Therefore, ICI 118, 551 is a valuable addition to the group of ß-selective adrenoceptor antagonists