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The partial agonist activity of xamoterol was evaluated by measuring changes in heart rate (HR) in pithed rats. Xamoterol showed dose-dependent positive chronotropic effects in catecholamine-depleted pithed rats (HR: 199 +/- 6 beats/min) and dose-dependent negative chronotropic effects in sympathetic nerve-stimulated pithed rats (HR: 325 +/- 16 beats/min). In contrast, isoproterenol exerted dose-dependent positive chronotropic effects in either condition (HR: 189 +/- 7 and 332 +/- 5 beats/min) and propranolol exerted dose-dependent negative chronotropic effects in either condition (HR: 209 +/- 5 and 344 +/- 19 beats/min). When exogenous noradrenaline was continuously infused into catecholamine-depleted pithed rats, xamoterol showed dose-related positive chronotropic effects with noradrenaline at 0.5 micrograms/(kg min) (HR: 235 +/- 4 beats/min), virtually no effects at 1.5 micrograms/(kg min) (HR: 297 +/- 11 beats/min) and dose-related negative chronotropic effects at 5 micrograms/(kg min) (HR: 330 +/- 5 beats/min). During continuous infusion of xamoterol [100 ng/(kg min)] into pithed rats, the control HR before stimulation was increased and the maximum increase produced by the sympathetic nerve stimuli at 0.25 to 4 Hz decreased. The maximum increase in HR brought about by xamoterol was about 71% of that induced by isoproterenol, and those by pindolol and practolol were about 40% and 21% respectively. It is concluded that xamoterol is a partial agonist with a strong agonist action.

The partial agonist activity of xamoterol(ICI 118,587) studied by heart rate response in pithed rats.