1. The effects of the beta 1-selective partial agonist
xamoterol and the full agonist
isoprenaline on rat cardiac beta-
adrenoceptors were compared in functional studies of heart rate response in vivo and in vitro. In addition, the ability of both agents to cause receptor down-regulation in the rat heart following chronic (6 days)
subcutaneous infusions was assessed by radioligand binding with [125I]-
pindolol. 2. In the functional studies,
xamoterol produced a maximal effect equivalent to approximately 65% of that of
isoprenaline and was overall less potent than the full agonist. 3. Compared to saline control, the density of beta-
adrenoceptors was reduced approximately 39% in ventricular membranes prepared from animals after 6 days of
isoprenaline infusion but was unaffected by
xamoterol. The relative proportions of the beta-
adrenoceptor subtypes were unchanged by either active treatment. 4. Plasma
xamoterol level at the end of the infusion period was equivalent to that associated with maximum
tachycardia in vivo and to the concentration producing maximal stimulation of the rat isolated atrium in vitro. Thus suggesting 100% beta-
adrenoceptor occupancy during the period of
xamoterol infusion. 5. These results indicate that in this animal model
xamoterol does not induce cardiac beta-
adrenoceptor down-regulation during chronic treatment, with doses that produce a maximal functional response both in vitro and in vivo.