β‐Adrenoceptor antagonist activity of 3‐methoxyisoprenaline

Abstract

1 The β-adrenoceptor antagonist activity of 3-methoxyisoprenaline, the O-methylated metabolite of isoprenaline, was studied on isolated driven atrial strip and tracheal chain preparations of the guinea-pig and on the hind limb blood flow of the dog. 2 On both the atrial strip and tracheal chain preparations the blockade of responses to isoprenaline fulfilled the criteria for simple competitive inhibition. 3 3-Methoxyisoprenaline decreased the vasodilator response to isoprenaline in the dog hind limb, but did not affect the response to noradrenaline. 4 3-Methoxyisoprenaline had about 1/3,700 of the potency of propranolol as a β-adrenoceptor antagonist on the tracheal chain preparation, 1/1,000 on the atrial strip preparation and less than 1/400 on the hind limb blood flow. 5 The antagonist activity of 3-methoxyisoprenaline showed a slight specificity for cardiac β-adrenoceptors, being 4.3 times more active on guinea-pig atria than on trachea. 6 Although 3-methoxyisoprenaline antagonized the actions of isoprenaline in the three preparations, its activity was extremely weak. It is unlikely that the formation of 3-methoxyisoprenaline from isoprenaline, administered therapeutically, could lead to β-adrenoceptor blockade.