A STUDY OF SOME PROPRANOLOL ANALOGUES FOR SELECTIVE β‐ADRENOCEPTOR ANTAGONISM USING pA2 VALUES ON ISOLATED TRACHEA AND ATRIA FROM GUINEA‐PIG

Abstract

1 pA₂ values for β-adrenoceptor antagonists were obtained on isolated preparations of guinea-pig trachea (intrinsic tone) and atria (rate), with isoprenaline, noradrenaline (β₁-selective) and fenoterol (β₂-selective) as agonists. Uptake mechanisms and α-adrenoceptors were inhibited. The antagonists studied were (±)-threo-α-methylpropranolol, (±)-1-(4-benzimidazoloxy)-3-isopropylamino-2-propanol (4-BIP) and (±)-1-(5-benzimidazoloxy)-3-isopropylamino-2-propanol (5-BIP). 2 4-BIP was a potent β-adrenoceptor antagonist but it was not selective for trachea (pA₂ on trachea 7.88 and on atria 7.73, fenoterol as agonist). 5-BIP was less than one tenth as active as 4-BIP and was therefore not studied in detail. 3 α-Methylpropranolol was potent and it was also selective for trachea (pA₂ on trachea 8.24 and on atria 7.56, fenoterol as agonist). This selectivity was not seen with isoprenaline as agonist. In tracheal preparations contracted by carbachol the slope of the Schild plot for α-methylpropranolol was less than 1.0 (isoprenaline as agonist). 4 α-Methylpropranolol, although not highly selective for β₂-adrenoceptors, is considerably more potent than the alternative β₂-selective antagonists available at present. Therefore, it may be useful in studies designed to classify β-adrenoceptor subtypes in tissues.