Effects of some imidazolidine alpha(2)-adrenoceptor agonists in rat isolated atria

1 The prejunctional alpha(2)-adrenoceptor agonist activity of four imidazol idines (UK14819, UK14304, UK15121 and UK11957) were compared to that of clo nidine in rat isolated atrial preparations. 2 The preparations consisted of spontaneously beating left and right atrial pairs that were incubated with [H-3]-noradrenaline. The efflux of radioact ivity induced by electrical field stimulation of intramural sympathetic ner ves was used as an index of neurotransmitter release and inotropic and chro notropic responses were recorded. 3 Two quinoxalinyl imidazolidines (UK14819 and UK14304 which have chloride and bromide substitution, respectively, in the phenyl moiety) caused decrea ses in the efflux of radioactivity with stimulation at 2 Hz and 10 Hz but n ot at 20 Hz. These effects were antagonised by the alpha(2)-adrenoceptor an tagonist idazoxan (0.3 mu M) but they were not affected by the alpha(1)-adr enoceptor antagonist prazosin (0.1 mu M). 4 The third halogenated quinoxalinyl imidazolidine analogue (UK15121, which has an iodide substitution in the phenyl ring) and a quinolinyl imidazolid ine (UK11957) have actions similar to clonidine. They decreased the efflux of radioactivity with stimulation at 1 Hz (for UK11957) or 2 Hz (for UK1512 1) and enhanced it at higher frequencies of stimulation. Both the inhibitor y and enhancing effects were antagonised by idazoxan but they were not affe cted by prazosin. 5 Unlike the other three imidazolidines in the present study, the quinoliny l imidazolidine (UK11957), caused a decrease in resting release of radioact ivity and this effect was prevented by the monoamine oxidase inhibitor parg yline (30 mu M). 6 These findings suggest that the 5-chloro-or 5-bromo substituted quinoxali nyl imidazolidines (UK14819 and UK14304) are full agonists at prejunctional alpha(2)-adrenoceptors, but the 5-iodo-substituted quinoxalinyl imidazolid ine (UK15121) and the quinolinyl analogue of UK14304 (UK11957), like clonid ine, appear to be partial agonists at these receptors.