Effects of some imidazolidine α2‐adrenoceptor agonists in rat isolated atria

1 The prejunctional α2‐adrenoceptor agonist activity of four imidazolidines (UK14819, UK14304, UK15121 and UK11957) were compared to that of clonidine in rat isolated atrial preparations. 2 The preparations consisted of spontaneously beating left and right atrial pairs that were incubated with [3H]‐noradrenaline. The efflux of radioactivity induced by electrical field stimulation of intramural sympathetic nerves was used as an index of neurotransmitter release and inotropic and chronotropic responses were recorded. 3 Two quinoxalinyl imidazolidines (UK14819 and UK14304 which have chloride and bromide substitution, respectively, in the phenyl moiety) caused decreases in the efflux of radioactivity with stimulation at 2 Hz and 10 Hz but not at 20 Hz. These effects were antagonised by the α2‐adrenoceptor antagonist idazoxan (0.3 μm) but they were not affected by the α1‐adrenoceptor antagonist prazosin (0.1 μm). 4 The third halogenated quinoxalinyl imidazolidine analogue (UK15121, which has an iodide substitution in the phenyl ring) and a quinolinyl imidazolidine (UK11957) have actions similar to clonidine. They decreased the efflux of radioactivity with stimulation at 1 Hz (for UK11957) or 2 Hz (for UK15121) and enhanced it at higher frequencies of stimulation. Both the inhibitory and enhancing effects were antagonised by idazoxan but they were not affected by prazosin. 5 Unlike the other three imidazolidines in the present study, the quinolinyl imidazolidine (UK11957), caused a decrease in resting release of radioactivity and this effect was prevented by the monoamine oxidase inhibitor pargyline (30 μm). 6 These findings suggest that the 5‐chloro‐or 5‐bromo substituted quinoxalinyl imidazolidines (UK14819 and UK14304) are full agonists at prejunctional α2‐adrenoceptors, but the 5‐iodo‐substituted quinoxalinyl imidazolidine (UK15121) and the quinolinyl analogue of UK14304 (UK11957), like clonidine, appear to be partial agonists at these receptors.