INTERACTION OF CLONIDINE, ITS METHYLENE-BRIDGED ANALOG, St 1913, AND THE BENZYLIC HYDROXYL-SUBSTITUTED DERIVATIVE, St 1965, WITH α1- AND α2-ADRENORECEPTORS

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Abstract
The effects of benzylic hydroxyl substitution on the activity of a close structural analog of clonidine was assessed at .alpha.1- and .alpha.2-adrenoreceptors both in vitro and in vivo to uncover possible differences that this substitution may have on the effects of imidazolines and phenethylamines at adrenoreceptors. In all test systems, the presence of the benzylic hydroxyl group was associated with a consistent and marked decrease in activity. These findings are in agreement with previous studies with imidazolines having different pharmacological profiles and different physicochemical properties than the clonidine derivatives reported herein. Apparently the deleterious effects of the benzylic hydroxyl group is ubiquitous among imidazolines, and is in marked contrast to the 100-1000 fold enhancement in activity that the benzylic hydroxyl substituent (i.e, .beta.-hydroxyl group) produces for the phenethylamines. Imidazolines and phenethylamines may interact differently with .alpha.-adrenoreceptors.