The new antihypertensive I 1 -receptor agonist (4) was rationally synthetized by the insertion of a phenyl group in the ortho position of the aromatic ring of the I 1 -selective antagonist (3). This "antagonismagonism" modulation, highlights the existence of expected analogies between I 1 -and α 2 -adrenoreceptor systems. Chirality proves to be crucial for the activation of I 1 -receptors, since the cardiovascular effects are produced exclusively by the (S)-(+)-4 enantiomer.