The in vitro pharmacology of xamoterol (ICI 118,587)

Open Access
Publisher Website
Google Scholar
Abstract
1 The effect of xamoterol and (-)-isoprenaline have been compared for their activity at β-adrenoceptor sites in a number of in vitro cardiac and smooth muscle preparations. 2 Xamoterol produced weak positive chronotropic effects in guinea-pig, rat and cat atria (intrinsic activity < 0.55, (-)-isoprenaline = 1). Positive inotropic effects were obtained in driven left atria of the cat but were absent in guinea-pig left atrial and right ventricular strip preparations. Agonistic effects were due to β1-adrenoceptor stimulation. 3 Xamoterol was without β-adrenoceptor-mediated inhibitory effects in guinea-pig ileal, tracheal and uterine preparations and in the rat vas deferens and oestrogen-primed uterus. Weak β2-adrenoceptor-mediated relaxation was obtained in progesterone-primed rat uteri. 4 Xamoterol produced non-specific inhibitory effects in guinea-pig ileal and tracheal preparations. 5 Xamoterol acted as a competitive antagonist at βr (pA2 range = 7.4 to 7.8) and β2-adrenoceptors (pA2 range 5.2 to 6.2) and displaced [125I]-iodocyanopindolol from guinea-pig left atrial (pKD = 7.25) and uterine (pKD 5.24) membrane preparations. 6 It is concluded that xamoterol displays a selective affinity for β1-adrenoceptors. Although its partial agonistic actions are more evident at β1-adrenoceptor sites, like prenalterol, xamoterol displays a degree of tissue rather than receptor-dependent selectivity.