Pre- and postsynaptic a-adrenoceptor blockade by (imidazolinyl-2)-2-benzodioxane 1-4 (170 150): antagonistic action on the central effects of clonidine.

While the specificities of alpha 1-adrenoceptor blocking agents are considered as satisfactory, those of alpha 2-adrenoceptor blocking agents are only weak. Therefore, a more selective alpha 2-adrenoceptor blocking agent is needed. In anaesthetized dogs and rats, (imidazolinyl-2)-2-benzodioxane 1-4 (170 150), a benzodioxane derivative, antagonized the pressor effects induced by adrenaline, noradrenaline and phenylephrine, but did not modify the effects of acetylcholine, histamine and isoprenaline. Therefore, its selectivity is satisfactory. In the anaesthetized dog, 170 150 (0.1 mg.kg-1) increased the tachycardia induced by electrical stimulation of the cardiac sympathetic nerve and antagonized the inhibitory effects of clonidine. In addition, 170 150 blocked and reversed some centrally mediated effects of clonidine such as the fall in blood pressure, bradycardia and reduction of splanchnic discharges in the dog, and the loss of the righting reflex induced by clonidine in the chicken. The centrally mediated effects of clonidine are attributed to stimulation of alpha 2-adrenoceptors; therefore, 170 150 appears to antagonize these alpha-adrenoceptors. Moreover, 170 150 appears to be more potent than piperoxan.