Effects of ring substitution on the pre- and postjunctional alpha-adrenergic activity of aryliminoimidazolidines.

The pre- and postjunctional alpha-adrenergic agonist potency of a series of aryliminoimidazolidines was determined in the isolated rabbit ear artery. This series included clonidine, an antihypertensive agent thought to act by stimulating brainstem alpha-receptors and known to be a preferentially prejunctional alpha-adrenergic agonist. Although all of the compounds acted preferentially on the prejunctional alpha-adrenoceptor, ring substitution had a dramatic effect on both potency and the degree of selectivity. 2-(3,4-Dihydroxyphenylimino) imidazolidine was both the most potent and most selective prejunctional alpha-agonist in this series.