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

The effect of xamoterol and (-)-isoprenaline have been compared for their activity at beta-adrenoceptor sites in a number of in vitro cardiac and smooth muscle preparations. Xamoterol produced weak positive chronotropic effects in guinea-pig, rat and cat atria (intrinsic activity less than 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 beta 1-adrenoceptor stimulation. Xamoterol was without beta-adrenoceptor-mediated inhibitory effects in guinea-pig ileal, tracheal and uterine preparations and in the rat vas deferens and oestrogen-primed uterus. Weak beta 2-adrenoceptor-mediated relaxation was obtained in progesterone-primed rat uteri. Xamoterol produced non-specific inhibitory effects in guinea-pig ileal and tracheal preparations. Xamoterol acted as a competitive antagonist at beta 1-(pA2 range = 7.4 to 7.8) and beta 2-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. It is concluded that xamoterol displays a selective affinity for beta 1-adrenoceptors. Although its partial agonistic actions are more evident at beta 1-adrenoceptor sites, like prenalterol, xamoterol displays a degree of tissue rather than receptor-dependent selectivity.