title: The partial agonist activity of xamoterol (ICI 118,587) studied by heart rate response in pithed rats.
abstract: 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.
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D003655:Decerebrate State / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017307:Xamoterol
chemical_list: D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D017307:Xamoterol; D009638:Norepinephrine