2-(aminobenzyl)-1,2,3,4-tetrahydroisoquinolines: A new class of α2-adrenergic receptor antagonists

Article abstract of DOI:10.1016/0223-5234(93)90130-7

A new class of α₂-adrenergic receptor antagonists, the 2-(aminobenzyl)-1,2,3,4-tetrahydroisoquinolines 4 and their derivatives, is described. Two synthetic routes are reported. An investigation of the structure-activity relationships including various substitutions of the isoquinoline moiety and the benzyl group is discussed. The affinity and selectivity for both α₁- and α₂-adrenoceptors was defined by studying the displacement of [³H]-prazosin (α₁-sites) and [³H]-yohimbine (α₂-sites) from rat brain membranes. The 2-(2-amino-3,4-dimethoxybenzyl)-6-methoxy-1,2,3,4- tetrahydroisoquinoline 4a presented affinity and selectivity close to yohimbine. In functional experiments the α-adrenoceptor blocking properties of 4a have been evaluated on isolated rat aorta and on the twitch responses of the isolated rat vas deferens.