A morpholinocatechol compound (UK42620) with clonidine- and tyramine-like actions

1 The actions of a morpholinocatechol (UK42620) were studied in rat isolated atria preparations consisting of spontaneously beating left and right atrial pairs. 2 UK42620 produced positive inotropic and chronotropic responses and, in atria that were incubated with [3H]-noradrenaline, it also produced a massive increase in the release of radioactivity. 3 These actions of UK42620 were similar to those of tyramine and were blocked by the β-adrenoceptor antagonist propranolol (0.3 μM) and by the neuronal uptake blocker desipramine (1 μM). 4 In the presence of desipramine, UK42620 but not tyramine produced a decrease in the stimulation-induced efflux of radioactivity that was antagonized by idazoxan. 5 Thus, UK42620 had prejunctional α2-adrenoceptor activity like that of clonidine- and tyramine-like activity releasing large amounts of noradrenaline.